Helen Baker, Director of Pharmaceutical Sci­ences, has been featured in Drug Development & Delivery's special feature article, "Outsourcing Formulation Development & Manufacturing: Understanding Critical Attributes Earlier in Development Leads to a More Robust Drug Product."

Formulation development and manufacturing outsourcing compress timelines and mitigate risk, enticing many pharmaceutical and biotech companies worldwide to partner with outsourcing service providers in the early phases of the drug development process. This has resulted in an economic impact on the global formulation development out­sourcing market, which is expected to reach a value of $31.8 billion by 2027, up from $21.1 billion in 2021

“Clients need to ensure they part­ner with a CDMO that has a good awareness of both material supplier lead times, availability of alternate merchants, and who have the expert­ise to offer up viable alternatives that would not impact the performance of the end product,” says Helen Baker, Director, Pharmaceutical Sciences, Quotient Sciences. “A CDMO capable of both preempting and adapting to supply chain issues, while maintaining the integrity of a comprehensive and thorough development plan will be most attractive to pharmaceutical clients.”

The pandemic also forced the in­dustry to pivot toward new therapeu­tics, particularly mRNA-based drugs. As a result, many CDMOs have in­vested in new facilities and state-of-the-art equipment focused on biologics manufacturing.

This annual, exclusive Drug Devel­opment & Delivery report describes how drug sponsors and CDMOs are collaborating earlier, highlights how third-party contractors are navigating material shortages, and discusses how the industry is shifting to address dif­ferent therapeutic targets and mole­cules, such as mRNA.

Quotient Sciences: Clinical Testing & Development Under One Roof

A recent formulation development challenge that Quotient Sciences faced in­volved a BCS class IV candidate des­tined for solid oral delivery. The molecule exhibited poor solubility and permeability, with erratic absorption as an inevitable consequence. Al­though numerous solubility enhance­ment techniques exist, a critical factor in development was to ensure that the dosage form selected must be consis­tent and scalable to a sufficient size to support a commercial campaign. 

Hot melt extrusion offered not only a vehi­cle for manipulating the absorption properties by allowing for the incorpo­ration of enhancement aids but was easily controlled and scaled-up, with the additional benefit of optional con­tinuous manufacturing. 

Continue reading the article

What technologies do you commonly use to generate fast, reliable data for drug development?

All the bioanalytical work is mass spectrometry-based, including liquid chromatography−mass spectrometry (LC−MS), gas chromatography−mass spectrometry (GC−MS) and inductively coupled plasma mass spectrometry (ICP−MS), which is one of our specialty areas. ICP−MS capability allows the team to measure elements that are very specific to a drug and there are very few companies who can offer a service as robust as ours.

On a practical level, how does integrating clinical pharmacology, bioanalysis and pharmacokinetics actually speed up clinical development times?

Time savings come in the form of efficiencies which are formed from the integration of services from Arcinova and Quotient Sciences.

Transfers of information and data move from being external to internal, allowing a set of agreed standard specifications/timelines (e.g. data transfer), being able to jointly track of samples, which will allow close coordination of delivery days to minimize white space/delays. All of which will be managed under a single quotient project manager for all services managing and driving the whole project timeline.

It also facilitates a much easier relationship with clients, with continuity of contacts, methods and templates, the same bioanalytical, pharmacokinetic, project manager, sample shipment/management contacts for clients throughout development.

Where do you see the future of the bioanalytical services industry?

Contract bioanalytical services will continue to grow to meet the market demands. Whilst historically, most large pharmaceutical companies traditionally performed their bioanalysis in house, that model has dramatically changed over the last 10 years, with the majority now performed by CRO’s. 

Consequently, the intrinsic knowledge and new generation of bioanalytical scientists now reside with the CRO’s, who can now leverage that to support both traditional pharma and emerging biotech companies, who’s knowledge in this field may be limited. 

As our knowledge spans both pharma and CRO, we are in an ideal environment to support and guide our clients and this demand will continue to grow. We continue to invest in both technology and people, so the future is assured.

Read the full article on Bioanalysis Zone

Low-volume drugs, such as orphan drugs, present challenges in achieving favorable production economics and in managing the projects themselves. A roundtable of CDMOs provides perspectives on those challenges and best practices to resolve them. 

Quotient Sciences experts contributed insight to this recent article with DCAT Value Chain Insights. Read what Dr. Paul Quigley, Principal Research Fellow, Drug Substance, and John McDermott, Executive Drug Development Consultant, had to share about developments in rare diseases.

Read the full interview

Q: What particular challenges arise from a supply planning/management perspective when working with low-volume drugs?

Paul: Most CDMOs are dependent on large-volume processes to achieve economies of scale. We take a material-sparing mindset when developing scalable manufacturing processes, which is particularly important for low-volume drugs.

Q: Any particular challenges when scaling up from clinical to commercial scale when working with a low-volume drug? 

John: If the process of scale-up is well understood and there are appropriate processes in place to manage the scale-up from clinical to commercial scale, this shouldn’t present a technical problem as by definition low-volume drugs sit somewhere along the scale spectrum. However, low-volume drugs require expertise in controlling processes at the intended scale, sometimes with equipment that can be difficult to find in late-stage and commercial production.

Nand Singh, Medical Director at Quotient Sciences, contributions to a bial study paper in the British Journal of Clinical Pharmacology, published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This paper documents the study, absorption, metabolism and excretion of opicapone (2,5-dichloro-3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor.

Aims: The absorption, metabolism and excretion of opicapone (2,5-dichloro3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor, were investigated.

Methods: Plasma, urine and faeces were collected from healthy male subjects following a single oral dose of 100 mg [14C]-opicapone. The mass balance of [ 14C]-opicapone and metabolic profile were evaluated.

Results: The recovery of total administered radioactivity averaged >90% after 144 hours. Faeces were the major route of elimination, representing 70% of the administered dose; 5% and 20% were excreted in urine and expired air, respectively. The Cmax of total radioactivity matched that of unchanged opicapone, whereas the total radioactivity remained quantifiable for a longer period, attributed to the contribution of opicapone metabolites, involving primarily 3-O-sulfate conjugation (58.6% of total circulating radioactivity) at the nitrocatechol ring. Other circulating metabolites, accounting for <10% of the radioactivity exposure, were formed by glucuronidation, methylation, N-oxide reduction and gluthatione conjugation. Additionally, various other metabolites resulting from combinations with the opicapone N-oxide reduced form at the 2,5-dichloro-4,6-dimethylpyridine 1-oxide moiety, including nitro reduction and N-acetylation, reductive opening and cleavage of the 1,2,4-oxadiazole ring and the subsequent hydrolysis products were identified, but only in faeces, suggesting the involvement of gut bacteria.

Conclusion: [14C]-opicapone was fully excreted through multiple metabolic pathways. The main route of excretion was in faeces, where opicapone may be further metabolized via reductive metabolism involving the 1,2,4-oxadiazole ring-opening and subsequent hydrolysis

Read the article

Champion Award Winning Categories:

• Expertise (Overall)
• Reliability (Overall)

Leadership Award Winning Categories:

• Capabilities (Overall)
• Compatibility (Overall)
• Expertise (Overall)
• Reliability (Overall)
• Quality (Overall) 

For the 2022 CRO Leadership Awards, we once again teamed up with ISR Reports to determine the award recipients. 50 contract research organizations were assessed on 20+ performance metrics in ISR’s annual CRO Quality Benchmarking survey.  Respondents only evaluate companies with which they have worked on an outsourced project within the past 18 months. This level of qualification ensures that survey responses are based on actual involvement with CROs and clear experiential data.

See the report & full list of winners

When it comes to Quality Assurance (QA), what are some of the major challenges that have been impacting the pharmaceutical industry lately?

The competition for high-quality QA professionals has always been an industry challenge, but since the pandemic, this has been exacerbated. With so many pharmaceutical companies competing for qualified candidates, turnover has increased, competition for resources is high, and compensation demands continue to rise. The job market has changed, with more individuals seeking work-from-home opportunities. Remote work can be difficult to offer for many QA roles in a clinical research organization (CRO) or a contract development and manufacturing organization (CDMO) where real-time, “on-the-floor” interaction is needed with clinical or manufacturing colleagues, and with customers and regulatory agencies.

Service providers that Quotient Sciences partners with have shared that they too are experiencing the challenges of turnover and high absenteeism. These strains can result in longer lead times, higher error rates, potential delays, and increased costs, which can impact the customer. At Quotient Sciences, we are focused on minimizing the impact that these challenges may have on our customers, and we strive to deliver the highest degree of quality for each program. We proactively take actions to minimize risks and conduct thorough investigations into any discrepancies, ensuring that corrections are implemented, and actions are taken to mitigate the potential for recurrence. 

The increased focus by many sponsors on developing new drugs that fulfill unmet medical needs or provide improved outcomes over currently available therapies has required CDMOs and CROs to seek ways to shorten timelines without compromising on quality or compliance. This in turn requires QA to drive quality system efficiency and support the delivery of integrated services aimed at reducing drug development timelines.  

In drug development and manufacturing, what role does Quality Assurance & Compliance play? What makes it so important, not just for the contract service provider or the sponsor but for the patient as well?

The Quality Assurance & Compliance function (herein termed “QA”) fulfill a number of crucial roles supporting drug development and manufacturing. QA is accountable for staying abreast of applicable global regulatory requirements and expectations and translating these into fit-for-purpose policies and procedures used by all colleagues to deliver safe and effective products. In a contract organization, QA also works with sponsors to ensure that their requirements are understood and integrated into any project-specific activities. QA maintains oversight of Good x Practice (GxP) work performed across the organization, ensuring that it is conducted in a compliant manner and serving as a coach and mentor for all colleagues to help ensure that they understand expectations and guide them on how to deliver quality in their roles. When quality issues arise, QA also serves as a risk manager. They collaborate with subject matter experts, which includes the sponsor, to evaluate risks and ensure the actions taken are commensurate with the level of risk, while consistently prioritizing the needs of the patient. The maximum effectiveness of QA’s role is best achieved when they serve as an engaged partner to the business, working collaboratively with all internal functions and externally with the sponsor, to proactively build quality into products and services. These actions ensure that quality and compliance objectives are integrated with business objectives, which benefit the contract service provider, the sponsor, and ultimately the patient. 

What keeps you up at night when it comes to some of the major Quality Assurance & Compliance predicaments in the drug development and pharmaceutical industry?

A few challenges that drug development organizations are facing today that keep me as a Compliance leader up at night include retention of a qualified workforce, the constant need for speed and agility, supply chain disruptions, and inflation and its impact on rising costs. 

Turnover is a major issue impacting our industry. To adapt to current workforce needs, employers are forced to reassess how work gets done. It is essential for businesses to respond quickly to retain their qualified workforce, but these types of changes must also be thoroughly considered so as not to create more business complexity or add long-term costs that cannot be effectively managed. The increased need for speed and agility in all aspects of operations adds additional strain on the workforce that can further compound the retention concern. 

Supply chain disruptions continue to impact the pharmaceutical industry. These challenges increased during the pandemic and have been further exacerbated recently due to other geopolitical events, resulting in delays in accessing materials needed to deliver drugs to patients in need and progress development of new drugs.  Organizations may need to quickly identify and qualify alternate materials or vendors, develop and qualify or validate new systems and processes, and deliver finished products under more stringent timelines. This is another example where speed and agility are essential but can also result in unanticipated errors. Quality management systems must be capable of facilitating agile working while still maintaining robust controls to detect deviations. 

Inflation and its impact on rising costs is another major challenge. Costs associated with materials, labor, utilities, and distribution continue to increase, which can impact an organization’s top-line growth and reduce cash needed for forward-thinking investments. Leaders must continue to seek opportunities to reduce costs, improve processes, reduce waste, and leverage technology to deliver products and services. Quality and compliance must remain a strong consideration when driving these improvements.    

Can you tell us about the latest quality systems or compliance project that you have been working on, and what are some of the technological and process elements that you leveraged to make the project successful? How will it benefit not only Quotient Sciences but also the customer?

One of the most significant recent investments in quality systems at Quotient Sciences was the implementation of an electronic document management system (eDMS) and quality management system (eQMS). Quotient Sciences recognized the need to establish an integrated quality management system that provided real-time visibility to documents and data, improved metric reporting and analysis, was easy to maintain, and was scalable to grow with our business. Veeva Vault was our chosen solution. 

Veeva has served as a common platform for harmonized processes across all Quotient Sciences sites, which include but are not limited to the management of controlled documents, deviations, customer complaints, change control, and corrective and preventive actions. These processes enable Quotient Sciences to deliver a harmonized customer experience and shorter response times. 

Since the implementation of Veeva in mid-2020, Quotient Sciences has continued to seek opportunities to expand system capabilities and continue our digital transformation of quality processes, with the focus on improving efficiency and effectiveness while maintaining compliance.

Which are some of the current and future technological trends that excite you in the Quality Assurance & Compliance arena that can better aid the drug development industry?

The drug development industry strives to remain on the cutting edge, continually seeking new or advanced therapies to fulfill unmet patient needs. Very few drugs that are in development make it to market. There is an immense amount of data produced for both successful and unsuccessful drugs alike. Seeing the emerging trend in industry to better utilize data to improve future drug development is incredibly exciting. 

Predictive analytics may be used to help predict drug performance, thereby potentially reducing timelines for new drug development and increasing the success of clinical trials, while reducing risks to volunteers and patients. This tool can also improve manufacturing process robustness, thus increasing supply chain reliability and reducing time to market. Overall, this can result in shorter drug development timelines, reduced costs, and higher success rates. It can also lead to better and more consistent product quality. Most importantly, predictive analytics can result in improved therapies being made available to treat patients sooner. 

The enormity of available data also supports advancements in data connectivity. Data silos have historically been common in drug development and manufacturing. Data resides in different sources that may be difficult to access and may not be easily combined with other data to provide a reliable holistic overview. Linking these separate data sets can help break down silos and improve delivery of the right data to the right people at the right time to support improved decision-making.     

Silos do not just exist in data. They have also been common across the supply chain, which can result in delays and disruptions in moving a drug through the development process. It is exciting to see companies, such as Quotient Sciences, who are offering integrated services that can shorten development timelines and costs to get drugs to patients faster. 

What Quality Assurance &Compliance standards should sponsor companies look for when selecting a contract service provider?

Prior to selecting a CDMO or CRO, sponsor companies should first seek to understand their own needs and priorities. Questions that sponsors should take into account include:

• To what extent are they looking to outsource versus manage internally?
• Are they looking for a company that has established systems and processes that will be used to execute the contract work, or will they be prescribing those processes? 
• Are they seeking a supplier for limited transactional work, or are they looking to cultivate a partnership that will span many projects?
• Are they seeking the lowest-cost service provider or one that offers differentiated services capable of managing complex programs? 

Once these needs are understood, the sponsor company should seek a partner with fit-for-purpose quality systems that provide flexibility, agility, and a strong compliance history. Other standards that sponsor companies should seek in their service provider include visible action-oriented metrics for quality, service, and delivery; a robust integrated Corrective and Preventive Action (CAPA) program with demonstrated effectiveness measures; and a robust quality management review program.  Additionally, sponsor companies should look for a contract service provider that is collaborative and promotes sponsor-to-provider, function-to-function (e.g. sponsor QA to provider QA) interactions. This will ensure open communication at the right levels between both parties while driving strong collaboration.

Read the full article here

Kimberly is an experienced compliance leader with over 25 years’ in life sciences.  Combining her technical and leadership capabilities, she works to identify creative solutions that balance compliance and business risk to achieve business results that meet regulatory expectations.  She has served in senior Quality leadership roles overseeing development, manufacturing, and distribution of pharmaceutical and medical device products supporting a broad range of therapeutic areas.  

Kimberly received her BS degree in Mechanical Engineering from West Virginia University, a MS degree in Engineering Science and an MBA from Penn State University, and a graduate certificate in Pharmaceutical and Medical Device Law and Compliance from Seton Hall Law School. 

Summary: In this article with Drug Development & Delivery, Dr. Andrew Lewis highlights the growing demand for modified-release (MR) dosage forms that deliver drugs at targeted gastrointestinal sites, maintain plasma concentration, and improve patient compliance. He emphasizes challenges in predicting human pharmacokinetics (PK) from nonclinical models and introduces the design space concept with on-demand manufacturing, applied through the Translational Pharmaceutics platform. This approach allows real-time formulation adjustments during clinical trials, reducing timelines and costs while mitigating development risk. Modified-release technologies like controlled-release, pulsatile, delayed-release, and gastro-retentive systems are evaluated using the Translational Pharmaceutics platform for optimized performance and efficient progression to commercialization.

Modified-release formulations are in high demand, but post challenges in development.

For formulators, they enable drugs to be released in the optimal gastrointestinal (GI) locations to achieve and maintain desirable plasma concentrations for extended periods, avoiding undesirable excursions outside the therapeutic range. For patients, modified-release formulations provide the convenience of infrequent dosing with potentially greater efficacy and fewer side effects than similar, immediate-release delivery systems.

An impressive variety of modified-release formulations are possible, thanks to ongoing technological developments. Strategic selection of excipients and delivery technologies can yield formulations that fulfil very specific performance requirements, such as gastro-retention and sustained-, pulsatile-, or delayed-release formats. Nonetheless, throughout the past 20 years, the fundamental methodology for developing these formulations has stagnated. Initial formulations continue to be founded upon in vitro and preclinical test results, despite evidence that these data correlate poorly with pharmacokinetic (PK) drug performance in humans. 

In this article with Drug Development & Delivery, Dr. Andrew Lewis addresses available modified-release formulation technologies, the challenges in modified-release formulation development, and the use of a formulation design-space with on-demand manufacturing. This methodology enables critical-to-performance formulation adjustments during clinical conduct, saving time and cost, and reducing risk in modified-release drug development. 

Modified-release formulations and the abundance of modified-release technology: A blessing and a curse

An ever-increasing number of polymers and formulation technologies allow finely tuned control of many aspects of drug release. Selecting and/or combining these technologies offers great potential for optimized oral drug delivery. However, managing all the variables and interpreting in vitro, preclinical, and available human clinical data to define a formulation strategy capable of achieving the desired PK performance is more difficult than many developers expect. Accurate performance prediction is crucial because miscalculations in planning for development or manufacturing are costly and often cause delays.

Off-the-shelf and proprietary polymers help developers achieve their PK goals. Certain polymers are better suited for sustained or delayed release and may be designed to deliver APIs to specific GI target areas, depending on physicochemical, biomechanical, and human physiological factors influencing the site of release. The range of solid dosage forms offers further layers of complexity. This ever-expanding array of tools makes many modified-release formulations possible. 

Each delivery format has its own idiosyncrasies. In the first instance, understanding the target PK profile is crucial. What plasma concentration-time profile does the formulation need to deliver? Experience and expertise are then required to select and implement a rational formulation program based on API characteristics, such as solubility, stability in stomach acid, particle size, and bioavailability. 

Furthermore, human physiology factors (such as an absorption window, drug transporters, enzymes in the GI tract, and intestinal motility) can impact a product’s performance as it transitions through the intestine. Given these variables, being sure the formulation performs in vivo as it did in vitro can be challenging. A good CDMO can help find the best approach and select a technology to achieve the desired performance. 

Continue reading this feature article on the Drug Development & Delivery website for more insight on the best way to predict a formulation’s clinical performance and using a formulation design space to evaluate modified-release technologies. 

Richard Castledine talks to Pharmaceutical Technology

Each molecule has unique requirements and challenges, and a variety of solutions for drug substance synthesis and manufacturing are available, so it is important to have a keen understanding of the strategies that can help streamline these processes

Drug substance plays a key part in ensuring a drug program achieves its major milestones, keeps to budget and delivers on its corporate goals. As every molecule and development program is unique, there is no single drug substance synthesis and manufacturing solution, so understanding what processes and technologies are available, what strategy is best, and who to partner with is key. 

To increase the likelihood of clinical success, drug developers must identify challenges and potential red flags early on in the candidate selection stage. This minimizes downstream risks, helps to determine a suitable synthetic route for scale-up, and facilitates an easier transition into the formulation development phase. As a result, pharmaceutical companies increasingly prefer to partner with contract development and manufacturing organizations (CDMOs) that have end-to-end capabilities, where knowledge sharing between process research and development (PR&D), analytical, and formulation teams leads to rapid parallel development and optimization of both drug substance and drug product. Placing traditionally siloed drug substance and drug product development activities within a single organization that also has commercial manufacturing capabilities accelerates clinical development and builds in quality and robustness of supply.

Timing is everything, and successful drug substance development and manufacturing depends on having the expertise, agility, and flexibility to solve any problem that may arise in a timely fashion. Quotient Sciences, a drug development and manufacturing accelerator, brings together a depth of knowledge, breadth of experience, and cutting-edge technologies to solve complex drug substance and drug product problems related to scalability, efficiency, and economy. They provide fully integrated drug substance, drug product, and clinical services spanning from candidate selection through commercial manufacturing under a single organization. This integration of services enables them to quickly identify challenges and develop solutions based on real-time data before they become bottlenecked, which in turn lowers the risk of timeline delays for their customers.

Important considerations for drug substance development

Polymorphic form issues

Understanding the polymorphism of a drug compound plays a key role in both drug substance and drug product development because it can negatively impact the downstream stability, solubility, and bioavailability of a drug. Polymorphic form changes are a frequent issue in drug development, so the key is ensuring only the desired polymorph is produced, otherwise, the consistent efficacy of the final drug can be affected by changes to its solid-state structure. A full analysis of the drug’s solid state will indicate its propensity to form various polymorphs.

These polymorphs all have the same chemical composition and synthetic route, but they have varied crystalline structures with different physical properties such as melting points. It is important that they are screened to select the best solid-state for formulation development and manufacturing. Recrystallizing the drug compound under different conditions will help determine the likelihood of the occurrence of varied thermodynamic and kinetic solid products.

Quotient Sciences uses computational modelling and simulation to narrow the field of polymorph possibilities, which acts as a predictive tool for choosing the right solid-state formulations to move forward into the clinic.

Applying real-time data

According to Richard Castledine, Head of PR&D, Drug Substance, at Quotient Sciences, “We are fortunate to have a wide array of state-of-the-art process analytical technologies (PAT) at our Alnwick, UK, facility, which we use to generate real-time data for processes that are under development. We are keen to increase the digitalization of our PR&D space, enabling us to make greater use of modeling predictive tools to make faster, better-informed decisions.”

“These tools help us understand more precisely the mechanisms by which impurity generation and reaction progression are occurring. When we couple that with other techniques, such as the design of experiments (DoE), we can develop a robust appreciation of the process design space and understand the parts of the chemical space that give consistent purity profiles and consistent yields, which in turn delivers consistent throughput,” says Castledine.

“PAT enables us to make use of software and artificial intelligence (AI) as a predictive control tool. This means that when we go into the laboratory, we are confirming those results rather than exploring the whole space. The benefits to the customer are that it significantly shortens development time and makes the whole process more cost-effective.”

Analytical method development

When developing a drug substance manufacturing process, considering the impurities that are produced is as important as the drug substance itself. “By carrying out analytical method development in parallel to the development of the active pharmaceutical ingredient (API) synthesis, we can readily identify and quantify new impurities, which informs the direction of work undertaken by our development chemists,” shared Castledine.

“This provides understanding from a very early stage of development about the fate of impurities and control points within the synthesis. It also means that timelines can be reduced, so that non-Good Manufacturing Practice (non-GMP) demonstration batches can be started as soon as the synthetic methodology is available and stability studies of the API can be initiated as soon as enough material has been prepared.”

Determining the best manufacturing process – traditional batch vs continuous flow

When evaluating a new synthetic route for a target molecule, one of the first decisions to be made is whether to employ a traditional batch-based synthesis or to make use of continuous processing methodology.  Both approaches offer advantages and disadvantages, and the optimum solution will vary on a case-by-case basis. Parameters to be considered are the rate of reaction, the volumetric efficiency of the process, and the presence of any heterogeneous, reactive, or high-energy materials in the reaction mixture.    

Quotient Sciences has access to large-scale batch and continuous processing assets and are able to design the optimum equipment set-up to match the chemistry of the transformation required rather than compromise the chemical process to fit the ubiquitous batch reactor. Where continuous processing options are the best match, they often offer increased process reliability, improved impurity control, greater compatibility with PAT, and a faster path to scale-up.    

Streamlined processes to reduce time to market for drugs

Integrated drug substance and drug product services

When asked about some key processes that Quotient Sciences provides to clients that help streamline drug substance development and reduce time to market, Castledine states that the key improvement is the drug substance to drug product integration.

“Within Quotient Sciences, we have fully integrated drug substance, drug product, and clinical testing services, which gives us the ability to break down traditional industry silos, allowing us to streamline the outsourcing process for our customers.”

“Integrating all activities under a single organization encourages better workflows and processes and builds close relationships between multidisciplinary experts. We pride ourselves on cross-functional communication and knowledge sharing, and our drug substance team members work very closely with our colleagues in formulation development and drug product manufacturing to ensure the best outcome for our customers’ programs,” he says.

“As soon as we start to develop an API, we begin having conversations about the quantities that are available versus what is needed for the clinical program. We also discuss formulation strategies, timelines/decision points, and the customer’s desired target product profile (TPP).”

“Drug substance team members also provide the characterization and screening data that is generated as part of API crystallization, to inform the formulation development team about how the API is likely to behave under certain conditions,” says Castledine.

“For drug substance chemists,” he says, “the most useful and valuable information is understanding what kind of polymorphs form under different conditions. This data is also critical for drug product formulation development because it can give an early indication of whether a molecule may or may not have stability or solubility issues.”

“Understanding a molecule’s behavior is key when trying to design a formulation for the clinic. Technology selection is based on the solubility and permeability of a compound utilizing the Developability Classification System (DCS), so the sooner that this data is available to a formulation team the shorter the lead time to a developed formulation,” he says.

“Typically, in the CDMO space, polymorph screening, drug substance, and drug product services are all conducted at separate organizations,” says Castledine, “in a siloed manner and at different times in the development lifecycle. However, at Quotient Sciences, we can screen polymorphs in-house and provide that data in real-time to both drug substance and drug product development teams to aid in the development of our clients’ programs. Having these capabilities within a single organization also allows us to make informed decisions based on emerging data and rapidly accelerate our customers’ development timelines.”

Quotient Sciences’ drug substance services

Quotient Sciences’ capabilities in drug substance services include:

• PR&D
• Analytical method development and validation
• Salt selection and polymorph screening
• Non-GMP, GMP, and commercial drug substance manufacturing
  Pre-formulation development
• DoE
• Thermal hazard and reactivity assessment
• Stability testing
• Proven acceptable range (PAR) and critical process parameter (CPP) determination
• Impurity identification and synthesis
• Genotoxic impurity (GTI) assessment
• Process validation
• Investigational Medicinal Product Dossier (IMPD)/Investigational New Drug Application (IND) preparation
• Technical investigations
• Freedom-to-operate (FTO) assessments

Developing workable API solutions

When asked about some issues Quotient Sciences has faced and solved as an end-to-end CDMO for clients, Castledine shared, “We worked on a project where the API was showing good data in terms of its efficacy, but the client was having significant difficulties developing a sufficiently soluble formulation.”

“We were tasked to develop a second-generation compound that would benefit from improved solubility. Alongside the development of the second-generation compound, we also undertook further formulation development work on the original molecule and were able to develop a workable formulation for the customer’s first molecule,” he says.

“The advantage to the customer was that they no longer had to switch to their backup candidate and were able to continue with their first-generation compound, which was more advanced in the development lifecycle. We have subsequently become the primary drug substance supplier to that client and are progressing the project through to commercial validation and supply under a single organization.”

When asked to describe a service that Quotient Sciences provides that is unique in the drug substance design and production field, he explains, “Our approach to integrating drug substance synthesis and drug product manufacturing reduces risks and overall client timelines.”

“Delivery of the first GMP batches of an API in development is typically on the critical path,” shared Castledine. “To address this, we streamline and integrate the activities leading up to this point to remove barriers and reduce timelines. We provide pre-approved analytical methods and manufacturing instructions to our GMP facility to initiate manufacturing. It is also helpful to have some stability data at this stage, either real-time or accelerated, to assign a retest period to the first batch of API at release.”

“Furthermore, our commitment to embracing new and emerging technologies means that we are at the forefront of innovation regarding drug substance synthesis, which allows us to access reaction conditions that are out of reach of many of our competitors. From a customer perspective, this means that we are able to pursue more innovative solutions, reducing overall costs and getting new medicines to market faster.”

In summary, there are many challenges and considerations that drug developers must be aware of before kicking off their drug substance program.  Having a clear understanding of your molecule and its behavior, along with selecting the best manufacturing process, will help guide decision-making, aid downstream development, and move your drug substance off the critical path. In addition, leveraging a partner with in-house drug substances, drug product, and clinical capabilities can provide significant efficiencies and increase the potential for both clinical and commercial success.

Read the original article

Nottingham Festival of Science and Curiosity 2022

The Nottingham Festival of Science and Curiosity is back with a renewed vigour for all things scientific and curiosity-inspiring and with a programme brimming with activities for all the family across the county. Celebrating its seventh anniversary, the festival will be running from 7-16th February. The festival is all about providing opportunities for people in Nottinghamshire to be inquisitive, ask questions and let curiosity lead the way!

Quotient Sciences, a Nottingham, UK based drug development and manufacturing accelerator, will be supporting the festival once again, continuing its commitment to help the festival get science out of the labs and into the everyday lives of local people. A group of volunteers from across Quotient Sciences organisation have been working with the festival team to develop exciting medicine-related activities for a local primary, FE college and for members of the public.

Peter Scholes, Quotient Sciences’ Chief Scientific Officer said “We’re delighted to be participating in the festival and have the opportunity to show our continued support for this important community event. As a local science-based business originating in Nottingham 30 years ago we recognise the importance of stimulating interest and to demonstrate the positive & valuable impact that science has on our everyday lives.

Among the Festival highlights is The Curiosity Show, reinvented from last year's Wollaton Watch, a series of five hour-long children’s TV shows broadcast live, 4-5pm on Notts TV, which will feature live science demonstrations, interviews and try-at-home activities, as well as exploring all things curious across Nottinghamshire. The festival magazine is back for a second year with a brand new look, exciting new content and a range of fun activities for all the family. 

Megan Shore, the festival producer said “We’re so excited to be able to work with Quotient Sciences to bring the festival back out into spaces across Nottingham and we’ve put together such an exciting lineup of activities, especially including some in-person workshops! We’re looking forward to engaging with new audiences, celebrating all the wonderful science happening in our region and hearing what people across Nottingham are curious about.”

For more information including detailed event listings please visit www.nottsfosac.co.uk and follow the Festival on Instagram, Facebook and Twitter @NottsFOSAC #FOSAC22 #CuriousNotts

----ENDS----

For more information, please contact Festival Marketing and Communications Lead Jaskirat Kaur [email protected] or Festival Producer Megan Shore can be available for interview.

About Quotient Sciences
Quotient Sciences is a drug development and manufacturing accelerator providing integrated programs and tailored services across the entire development pathway. Cutting through silos across a range of drug development capabilities, we save precious time and money in getting drugs to patients. Everything we do for our customers is driven by an unswerving belief that ideas need to become solutions, and molecules need to become cures, fast. Because humanity needs solutions, fast.  For more information visit www.quotientsciences.com.

Nuformix plc (LSE: NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, is pleased to announce that following the Company's signing of an exclusive global licensing agreement with Oxilio Ltd ("Oxilio") for NXP001 on 13 September 2021, Oxilio has progressed the product and signed a significant service contract with Quotient Sciences Ltd ("Quotient Sciences") to support the formulation development of NXP001. NXP001 is a proprietary new form of aprepitant which is currently marketed for cancer chemotherapy induced nausea and vomiting ("CINV").

Under the contract Oxilio will work with Quotient Sciences, a drug development and manufacturing accelerator, to identify and evaluate the cocrystal formulation of aprepitant to deliver optimal bioavailability for the treatment of CINV.

Quotient has prior experience of working with the Nuformix NXP-001 co-crystal and previously developed a capsule and a powder for oral suspension formulation, evaluating its performance in a relative bioavailability study versus EMEND (a branded aprepitant).

Quotient will prepare for Oxilio CMC (chemistry, manufacturing and controls) batches and stability data to support a clinical trial application for the new formulation of NXP001.

The Company looks forward to providing further updates on Oxilio's progress with NXP001 in due course.

Commenting, Alastair Riddell, Executive Chairman of Nuformix, said: "We are very pleased to see the progress Oxilio is making with NXP001. Under the exclusive licence we signed with Oxilio we received an upfront payment, expect to receive milestone payments when the product completes clinical trials and ultimately royalties on any sales. This arrangement is allowing Oxilio to progress NXP001 without cost to the Company whilst we focus on progressing our two lead assets, NXP002 and NXP004. In relation to NXP002 and NXP004 we continue to make significant progress and I look forward to making further announcements in due course."

About Oxilio 
Oxilio is a privately held pharmaceutical development company focused on repurposing known drugs for the treatment of cancer through a programme of corporate alliances coupled with rapid proof of concept clinical development. Oxilio will develop and seek to exploit NXP001 globally for the treatment of cancer. It is focused on alleviating the current dilemma of a shortage of effective drug candidatesthat have potential as new cancertherapies- by adopting a drug repurposing strategy (identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication). The major advantage of this approach is that the pharmacokinetics- pharmacodynamics and toxicity profiles of these drugs are already reasonably well established. Thus- drug repurposing is a less risky development route with substantially lower associated development costs. The agreement with Nuformix allows Oxilio to focus on developing rapidly a unique formulation and dosage form with NXP001 and progressing into the clinic. For more information- please visit www.oxilio.co.uk.

About Nuformix
Nuformix is a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing. The Company aims to use its expertise in discovering, developing and patenting novel drug forms, with improved physical properties, to develop new products in new indications that are, importantly, differentiated from the original (by way of dosage, delivery route or presentation), thus creating new and attractive commercial opportunities. Nuformix has an early-stage pipeline of preclinical and Phase I-ready assets with potential for significant value and early licensing opportunities. https://nuformix.com/

About Quotient Sciences
Quotient Sciences is a drug development and manufacturing accelerator providing integrated programs and tailored services across the entire development pathway. Cutting through silos across a range of drug development capabilities, we save precious time and money in getting drugs to patients. Everything we do for our customers is driven by an unswerving belief that ideas need to become solutions, and molecules need to become cures, fast. Because humanity needs solutions, fast.