Paul Quigley recently shared thoughts on the importance of flexibility, collaboration and innovation for the modern CDMO with Contract Pharma.
In the featured article, Paul explains the greater need for more effective process solutions during drug development and how successful contract service organizations are meeting this challenge. He also defines the Quotient Sciences model for accelerated delivery, through integrated services and technological innovation.
Quotient Sciences won the Outstanding Achievement Award at the 2019 Medilink UK Healthcare Business Awards.
The Medilink UK Healthcare Business Awards recognize organizations that have made significant contributions to life sciences and who have excelled in their categories across the healthcare industry. Winners were chosen from an exclusive shortlist comprised entirely of winners from each of the regional Medilink awards.
The Outstanding Achievement Award recognizes the Company's momentous success and continued development. Quotient Sciences has experienced significant growth and global expansion following a series of acquisitions and facility investments in the U.K. and the U.S. and now employs over 850 employees across six operating sites.
Mark Egerton, CEO of Quotient Sciences said, “We are delighted to have won the Outstanding Achievement award. It is a great recognition for all the hard work and continuous commitment and dedication of our staff. Well done to the team for delivering this success."
Quotient Sciences was also recognized for its innovative approach to drug development, Translational Pharmaceutics®, which enables significant shortening of drug development times and reduced costs for biotechnology and pharmaceutical clients throughout the world.
The award recognizes UK companies that have made significant investments across the Atlantic in the last year. 32 companies, including Quotient Sciences, were recognized.
Quotient Sciences' US investment included the opening of a state-of-the-art, 45,000-square-foot facility located near Philadelphia, in Garnet Valley, PA. The $15 million investment is helping to build a Centre of Excellence for early-phase formulation development and clinical trial manufacturing.
“Our new facility was built in response to increasing customer demand,” said Mark Egerton, CEO of Quotient Sciences. “The site was specifically designed to optimize our ability to work with highly potent and poorly soluble molecules that dominate the industry pipeline. The facility also increases our capacity to provide integrated Translational Pharmaceutics® programs in the U.S., which deliver substantial benefits to customers including cost savings and reduced timelines to achieve proof-of-concept.”
The award was presented to Gordon Cameron, CFO of Quotient Sciences, during a ceremony held in London.
As an integrated drug substance developer, Quotient Sciences has the ability to solve the complex problems that its customers face. Gareth Jenkins and Paul Quigley shared their insight in this latest article with Chemistry World.
As an industry, we are seeing an influx of complex compounds identified during drug discovery that create greater challenges than ever before. In order to enable new ways to rapidly bring new drugs to market, contract development and manufacturing organizations (CDMOs) are increasingly being sought to consult on or investigate solutions to these challenges. Quotient Sciences' scientific experts work as detectives in drug development. Working together with our customers, we cut through traditional industry siloes to solve challenges related to scalability, efficiency, and economy in drug development.
Finding solutions to the biggest challenges faced during drug substance development relies on properly integrating analytical and production expertise.
The article, featured in the Chemistry Detectives issue, explores how solutions are found to enhance scalability, efficiency, and economy. It provides details on how metabolic and pharmacokinetic studies are used to determine drug compound fate and how our solid-state team investigates physical forms.
Quotient Sciences (“Quotient”), a leading drug development services and manufacturing organization, is pleased to announce that its Vice President of Pharmaceutical Sciences, Andy Lewis, has been appointed as Secretary of the Controlled Release Society (CRS).
CRS is the world’s leading scientific society, established to promote delivery science and technology, and is dedicated to the science of controlled release. The CRS serves members from more than 50 countries, with two-thirds of CRS membership representing industry and one-third representing academia and government.
Dr. Lewis has over 20 years of experience in the pharmaceutical and drug delivery industry. He currently leads a team of 120 scientists working on formulation development, clinical manufacturing, and pharmaceutical analysis projects. Dr Lewis is dedicated to overcoming drug delivery challenges, including solubility enhancement, controlled release, and transmucosal delivery of proteins and peptides. He is a member of the Academy of Pharmaceutical Scientists of Great Britain where he served on the Membership Committee and Board of Scientific Advisors, and for four years was Director-at-Large of the CRS.
Dr. Lewis will commence his service to the Controlled Release Society following the conclusion of the 2019 CRS Annual Meeting & Exposition held in Valencia, Spain, July 21-24, 2019.
According to the Pharmaprojects Pharma R&D Annual Review 2018, this expansion has been concentrated in Phases I and II more so than in late-phase development with over 2,000 new therapeutic molecules entering clinical research in 2018.
To address this growing need, Translational Pharmaceutics® helps accelerate timelines and reduce costs in drug development. This innovative approach helps drug developers reach milestones quickly and efficiently for first-in-human studies, drug product optimization, and integrated ADME programs.
Despite increases in spending, the industry struggles with poor R&D productivity. Outsourcing has become more siloed, with separate vendors focusing solely on discovery chemistry, discovery biology, preclinical toxicology and safety, clinical testing, or formulation development and manufacturing.
In the conventional outsourcing approach, the developer engages with multiple vendors, creating both a management burden and gaps in the development timeline. The contract development & manufacturing organization (CDMO) and the contract research organization (CRO) operate in separate worlds, with limited shared knowledge and no operational synergy between vendors, making it difficult for the pharma company to build efficiencies into the drug development process.
The early stages of drug development have been proven to be amenable to an integrated platform that ties together formulation development, real-time adaptive manufacturing, and clinical testing.
Integration of the “make” and “test” supply chains allows drug products to be manufactured to GMP within days of dosing, rather than weeks or months when using conventional processes. By using 14-day “make-test” cycles, a drug product is manufactured and dosed, clinical data are generated (for example safety, pharmacokinetic, pharmacodynamic, or biomarker), and then a decision is made on how to modify the drug product, formulation composition or dosage strength for the next study period.
Implementing a Translational Pharmaceutics® approach can trim six months or more from a typical drug development timeline. As well as immediate cost savings in early development, for a drug product forecasted to generate $500 million to $1 billion in annual revenue, such efficiencies can increase future revenue potential by millions of dollars per day.
In addition, given Translational Pharmaceutics® enables development decisions to be made based on clinical data rather than surrogate in vitro or preclinical data, the program maximizes the potential for success, avoiding the time and cost of potentially repeating multiple rounds of development cycles.
Large CDMOs typically insist on larger than required minimum batch sizes for drug product manufacturing; however, a flexible and adaptive manufacturing approach, tailored to the clinical trial, can reduce API consumption by >85%. That is a significant advantage in early development where API is produced at a small scale and must be carefully rationed to cover numerous activities.
Outsourcing these functions to a single partner that offers integrated capabilities as a single program of work, managed by a dedicated project manager, can significantly ease a sponsor’s management burden and contracting responsibilities.
Read case studies providing examples of how Translational Pharmaceutics® integrated programs have helped both small biotechs and large pharma clients alike overcome development challenges.
In 2018, we were involved in 14 scientific posters, 10 podium presentations, and 5 peer-reviewed publications. We are grateful to our customers who have been willing to have their work published and to all of the scientists involved in the design and delivery of these projects. Sharing the information with the wider pharmaceutical development community will help our collective goal of accelerating the delivery of new medicines to patients around the world.
For more information on any of our services or scientific research, contact us today.
Presented at AAPS
Presented at the European Padiatric Formulation Initiative (EuPFI)
Presented at the North American Cystic Fibrosis Conference (NACFC)
Presented at the American College of Allergy, Asthma & Immunology Conference (ACAAI)
The search for new therapeutic treatments has unveiled a class of compounds known as High-Potency Active Pharmaceutical Ingredients (HPAPIs), whose current market size (as of 2019) was approximately $17 billion and is expected to increase to $25-30 billion over the next 5-7 years1.
HPAPIs produce a response, or pharmacological effect, at a very low dose and offer benefits in numerous areas such as oncology drug development.
It is essential to understand the hazards posed by any new drug compound before its handling or manufacturing, but it becomes more important for HPAPIs due to the risks associated with potential exposure. There is often an incomplete toxicology package available for new compounds at the early stages of drug development to make proper safety assessments. In such cases, the compound is evaluated for factors including but not limited to carcinogenicity and cytotoxicity, source of origin (synthetic/semi-synthetic/biologic), targeted disease and mode of action, preferred dosage form and estimated dose if known, and physicochemical properties.
To ensure safe handling, pharmaceutical scientists and manufacturing technicians who work with HPAPIs must be suitably protected, and there must be rigorous controls and procedures in place at the facility where HPAPIs are handled. It's critical to have procedures in place to minimize cross-contamination among products made in the manufacturing facility. In some cases, personnel may also be placed under medical monitoring to ensure their long-term safety from any future, untoward effect.
We use a five-band system called the “Performance-Based Level of Exposure Classification," or PBLEC, to categorize a compound in one of five bands.
PBLEC 1 is the least potent compound, offering no pharmacological activity, to PBLEC 5, which is highly potent, toxic, or with high pharmacological activity. To meet safety and regulatory expectations, we routinely check our containment procedures and processes to mitigate cross-contamination risk and adopt best practices in the handling of HPAPIs.
We ensure that there is no cross-contamination through the implementation of various procedures based on source (by elimination and protection), risk (by reduction), and vulnerability (by engineering and administrative controls), such as:
Working with a CDMO who has a long track record of successfully handling HPAPIs is essential.
Contact us today to learn how we can help your next program.
References:
1. N. Walker, HPAPI Market Trends, 2018, https://www.contractpharma.com/issues/2018-09-01/view_features/hpapi-market-trends/
2. Bornett D., Pharm. Technol., 2008 (4) Supplement (2008). http:// www.pharmtech.com/high-potency-apis-containment-and-handling-issues
In early development, the first-in-human (FIH) clinical trial is often a single-center study and typically involves dosing a small number of healthy subjects over a short duration of days or weeks. In this study, the drug is administered in increasing doses and as such, a “fit-for-phase” drug product with high dose flexibility is often used, such as a simple solution, suspension, or powder-in-capsule.
This type of drug product can usually be prepared on-site, at a small scale, and with limited stability studies and analytical release testing. Simple pharmacy preparations may be sufficient for FIH clinical studies, but when moving beyond Phase I into later stages of clinical development, these products are unsuitable for both patient convenience and scalability to meet larger batch size requirements for Phase II trials.
Subsequent Phase II and Phase III patient trials involve a larger number of patients and often take place at multiple clinical sites, across states and countries, and over a longer period. To support these trials, the development team will need to bridge to an optimized drug product, such as a solid oral dosage form like a tablet, to ensure patient compliance and suitability for shipping globally. Product batch sizes manufactured to support Phase II and Phase III trials will need to increase to support the increased number of patients. If the molecule is successful in clinical studies, batch sizes will be scaled up to meet the demand for a commercially approved product.
Requirements for different product formats at each stage of development can result in delays and budget overruns when it comes to product optimization and scaling up. Sometimes, CMC delays can be prevented by careful planning, and integrating development activities and technology considerations in the formulation design process.
To improve R&D productivity and bring new molecules to market as quickly as possible, drug companies are actively seeking new ways of streamlining drug development using alternative outsourcing models. At Quotient Sciences, we coordinate drug product manufacturing requirements with a clinical development plan, to make and test formulations in a streamlined fashion. This leads to significant time efficiencies and cost savings.
Druggability Technologies (DRGT; now Tavanta Therapeutics) was a specialty pharmaceutical company dedicated to the development and commercialization of high-value proprietary drugs to deliver measurable improvement in clinical utility. They used the Quotient Sciences Translational Pharmaceutics® platform to advance the development of DRGT-46, a fast-acting formulation of celecoxib.
Clinical data was able to help DRGT drive formulation selection in real-time, allowing the company to efficiently bridge from a Phase I drug product to a dosage form suitable for patients in late-stage clinical trials. Continue reading the DRGT-46 case study to learn more about how Translational Pharmaceutics® was applied.
When you are looking for a partner who can help develop your drug product from first-in-human through to proof-of-concept and beyond, rely on Quotient Sciences. Contact us today to get started with your program.
Summary: Dr. Vanessa Zann explores strategies for modified-release formulation development, highlighting technologies such as controlled-release, multiparticulate systems, and osmotic delivery. She explains how Translational Pharmaceutics® integrates formulation design with real-time clinical PK data to overcome prediction challenges and reduce development risk. This adaptive approach ensures optimized drug performance and efficient progression from early development to commercialization.
For decades, modified-release drug products formed part of a line-extension category and were launched in a strategic way to offer a better product relative to commercial immediate-release products, thereby extending the life of the brand.
Today, pharma and biotech companies are increasingly considering modified-release technologies earlier in the development process of a new chemical entity (NCE) to obtain greater differentiation against other products in development or on the market. All stakeholders including investors, patients, doctors, and payors welcome this trend, especially where clearer therapeutic benefits are shown.
Many drug product improvements can be achieved using modified-release technology. Some examples include:
The benefits of modified-release products are significant but can come with technical challenges that prevent or complicate their development. When evaluating a modified-release product opportunity, we often start with two fundamental questions:
Modified-release formulation approaches range in complexity, and the formulation selection needs to be based on the properties of the drug substance and the target drug release profile. R&D programs can encounter large delays and cost overruns when the wrong modified-release technology and development plan are selected.
Our experience in the development of modified-release products spans numerous modified-release technology platforms: controlled release, gastro-retentive, delayed release, pulsatile, and biphasic release.
A variety of modified-release formulation technologies are available to be manufactured using common tableting, encapsulation, and coating processes (either pan or fluid bed coating). The specific modified-release behavior is also determined by the functional excipients used.
A common approach is to use hydrophilic polymers in a tablet that form a gel matrix in in-vivo that controls drug release out of the matrix. Polymer coatings are also applied either on tablets or multi-particulates, for example using beads, with functionality that may be pH-dependent. An erodible coat, or a coat that controls drug diffusion through a semi-permeable coat or orifice, may also be used. Both the excipients and the final products used are generally non-proprietary.
Among the more complex modified-release technologies are osmotic tablets, using the approaches described and sometimes also including a small orifice that contributed to release-rate control, and gastro-retentive formulations that apply a range of swelling, floating, or adhesion methods to delay gastric-emptying of the dosage form.
A traditional approach to screen and selecting formulation prototypes begins with in vitro testing and animal models, and then a lead prototype or prototypes are selected for clinical testing. This approach and overconfidence in non-clinical to clinical predictions can be flawed when developing oral modified-release formulations because the behavior of the modified-release formulation is highly dependent on human physiology and this dependence occurs over a longer duration of drug release.
Across modified-release drug programs, we often see that clinical performance of modified-release products differ considerably from in vitro or animal test predictions. This often provides a surprise for the drug development team but confirms why non-clinical tests should not be the backbone of a modified-release product development program.
Using Translational Pharmaceutics® allows us to make formulation adjustments in response to human PK data during the clinical study to accelerate development timelines. Using a science-driven approach, we are able to help clients derisk drug development. For more insight about this topic, watch our webinar on-demand: Non-Clinical vs Clinical: Risks & Considerations When Developing Modified Release Dosage Forms.
