The life sciences and pharmaceutical markets are ever-changing and constantly adapt to patient needs and global trends. Those along for the ride have experienced many so-called “revolutions” in the industry: the launch of the Human Genome Project in the 90s, the global push for digital health initiatives, and the previous surge in blockbuster drug approvals, among others. Each of these altered the market in their own significant way, but the latest revolution may the greatest yet: a complete paradigm shift in the way companies view patients.
A transformation is underway in medicine. One-size-fits-all treatments are increasingly sharing market space with targeted precision therapies. In 2018, the Food and Drug Administration (FDA) approved a record number of precision medications, and in 2015 more than a quarter of new drugs approved were precision medicines1. The future is also bright, as an estimated 40% of treatments in development are precision drug treatments (Figure 1)2.
The rise of precision medicine is altering how formulators approach new product development and patient care. Instead of looking to treat a large population with one blanket therapy, pharmaceutical companies are shifting to a more patient-centric approach that considers factors unique to an individual. Leading life science companies have nearly doubled their investments in precision and personalized medicine in the last five years and this is expected to increase by over 33% through 20231.
But … is the industry prepared?
“The rise of precision medicine is altering how formulators approach new product development and patient care.”
What is Precision Medicine?
Precision medicine (also known as personalized medicine) is healthcare designed to optimize a therapy for a particular group of patients, especially by using genetic or molecular profiling. For example, multiple commercial oncology medications are prescribed based on the expression of particular biomarkers3:
- Herceptin®(trastuzumab): targets HER2+ breast cancers, which have a higher number of HER2 receptors than normal cells
- Gleevec® (imatinib mesylate): targets Ph+ chronic myeloid leukemia, which exhibit the Philadelphia-chromosome DNA mutation
- Zelboraf® (vemurafenib): targets late-stage melanomas with the BRAF V600E DNA mutation
Precision Medicine vs Personalized Medicine: What’s the Difference?
Precision medicine and personalized medicine are essentially the same. The term “personalized medicine” was coined in 1999 to describe tailored treatments for specific patients or groups of patients. But the concept is seen in literature dating as far back as the 1960s4.
In 2011, the United States’ National Research Council (NRC) published a report on the subject titled Towards Precision Medicine. In the report, the NRC outlined how research and clinical data on tailored therapies could be captured in a “Knowledge Network” to be shared in the scientific community. The NRC also suggested that “precision medicine” is a more accurate way of describing this segment of the pharmaceutical industry, stating5:
“Precision medicine refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease… or in their response to a specific treatment.”
Since this report, the use of “precision medicine” has grown. In 2015, the White House unveiled its Precision Medicine Initiative, a $215 million investment to “leverage advances in genomics, emerging methods for managing and analyzing large data sets while protecting privacy, and health information technology” for the development of targeted therapies6. Today, “precision medicine” remains the more popular terminology, though personalized medicine, individualized medicine, and theranostics (a combination of therapeutic and diagnostic information) are all frequently used in this space.
Trends in the Pharmaceutical Manufacturing Landscape
Up until recently, the pharmaceutical industry has been locked in the pursuit of high-volume, best-selling drugs, and for obvious reason – a typical “blockbuster drug” generates at least $1 billion in annual sales. Focused on blockbusters, development and manufacturing capabilities in the pharmaceutical industry have evolved to meet the demands of high-volume product lines. Outsourcing partners followed suit, as the industry also looked to contract development and manufacturing organizations (CDMOs) for production assistance.
Uncoincidentally, we also began to witness trends of outsourcing consolidation and the emergence of mega-CDMOs capable of producing high volumes of commoditized products. Capacity growth served the demands of the blockbuster drug era – for example, statins, a best-selling drug category, are prescribed to 15 million people in the United States alone and millions more worldwide, meaning they require large volume production1.
The situation is quite different for precision therapies, which typically have patient populations of around 200,0007. Additionally, the active pharmaceutical ingredients (APIs) and formulations developed for precision drug products are often drastically more complex and require specialized handling. Due to blockbuster industry trends, very few CDMOs are equipped to meet the needs of these smaller-scale complex drug products. In the following sections, Dr. Robert Lee, President of the CDMO Division of Lubrizol Life Science Health (LLS Health), will outline exactly what you should look for in a precision medicine development partner.
What Should You Look for in a Precision Medicine CDMO?
Smaller scale production
First and foremost, a developer needs a strategy for small batch manufacturing of personalized medicines. Oftentimes the most economical and risk-adverse way to approach drug product development and eventual production is by partnering with an experienced outsourcing organization. While some large pharma companies may technically have the capacity to keep this work in-house, the small batch size requirements in precision therapies often make this impractical; the legacy model of single-product lines will ultimately result in unused time and equipment, translating to wasted dollars.
More and more products are coming out of smaller biotech companies and start-ups, which are unlikely to find ownership of their own production lines cost-effective and rarely consider manufacturing a core competency. 64% of US drug approvals in 2018 came out of emerging pharmaceutical companies versus the top ten giants that have historically dominated the market8. Therefore, the most practical approach with precision medicine is to enlist the help of a CDMO with expertise developing and manufacturing complex drug products with smaller batch size requirements.
LLS Health has decades of experience working with differentiated products, such as those for personalized medicine. According to Dr. Robert Lee, “We have a unique understanding of the many challenges precision therapies can present, and are very familiar with these types of products. With us, you never have to worry about ending up at the bottom of the queue as you compete against larger scale projects—as we have heard from some clients who previously used mega CDMOs. This year we launched our new commercial manufacturing facility, which was purpose-built for small-volume, high-value products, especially those that require special handling like precision drug treatments.”
Personalized approach for personalized medicines
In addition to small-scale production, a product developer should ensure their partner is decidedly flexible in their approach. Precision therapies are unique to a patient or patient population, so your CDMO should follow a methodology that is unique to your project as well. Make sure the organization you choose to work with is not only of the right size for your product but is also able to adapt quickly when troubleshooting and optimizing the critical quality attributes of your product. This flexible approach can be difficult to find at large CDMOs.
Despite their often-inflexible approach to development and manufacturing, many pharmaceutical companies still lean towards partnering with large CDMOs due to the perception of reduced supply chain risk or greater stability. With critical products such as precision medicines, ensuring stable commercial supply for a drug product is crucial. Therefore, the key is finding a healthy balance of the necessary qualifications in a development partner—the right size, production capability, flexibility, and company stability.
“At Lubrizol, our approach is never one-size-fits all but is instead centered around the physicochemical properties of your chosen API and individual project needs,” Dr. Lee comments. “We also offer stable commercial supply for your product. The CDMO Division of LLS Health is a smaller-scale facility of around 100 industry experts, but we are also part of Lubrizol Life Science, a Berkshire Hathaway company, and benefit from the security that a large organization like this provides.”
Seamless production and efficiency
It is particularly crucial that your development and manufacturing partner for precision treatments possesses the facility and equipment necessary to seamlessly progress you from preclinical to clinical development and eventually to commercial production. Choosing an appropriately-sized one-stop-shop minimizes the time and risk between the various stages of your program and increases the chance of success for projects such as personalized drug therapies.
“Precision medicines often utilize specialized manufacturing processes. LLS Health is equipped with flexible facilities to transfer in proprietary technologies and custom equipment trains for GMP production.”
These products often require a wide breadth of specialized equipment and services due to their inherent complexity and the fact that many them are biologics. This can include analytical and biopharmaceutical testing, lyophilization capabilities, sterile fill-finish/aseptic processing, and highly potent compound handling, among others. It is rare for a single CDMO to have one-stop shop capabilities while still accommodating the flexibility and batch sizes required of precision medicines.
“Being able to smoothly take a project from its very early stages all the way up to commercial production is crucial – it will doubtlessly save you money, time, and significant frustration, and that’s truly important to us at LLS Health. With personalized medicines, it is difficult to find a full-service outsourcing partner – and that became our driving force when designing our new commercial manufacturing facility,” notes Rob on the company’s recent expansion. “From our 120 ft2 lyophilizer and large ISO 7 clean room space to our extensive expertise in micro- and nanoparticulate formulation and biological compound handling, we have purposefully set ourselves up to be the perfect fit for drug products like precision medicines.”
The age of personalization is upon us, and the pharmaceutical industry is not excluded. However, development of precision medicines represents a departure from previous norms, and the industry is still evolving to meet these new, customized needs. Pharmaceutical manufacturing historically has been characterized by large batch production with simple APIs and processes. Personalized medicines, which are typically more complex than conventional drugs, simply cannot be produced this way. Therefore, choosing a partner with very specific qualifications is crucial to your success.
Precision therapies require just that – precision. To attain the high level of efficacy, safety, and reliability necessary for these types of products, you need a CDMO that has a proven track record and specializes in producing small quantities of complex products. Whether you choose to explore your options with LLS Health or another CDMO, be sure to keep in mind the size of the organization, how they approach your individual needs, and their experience in the field.