The complexity of clinical trials has increased in recent years, bringing new challenges and risks that could impact success. In this article, Robert Feltz, Director of Analytical and Formulation Services at Sharp Clinical, shares his unique insights into the factors driving drug developers to outsource their formulation, analytical testing, and manufacturing to expert organizations that can offer support with integrated services. He also emphasizes the importance of leveraging contract pharmaceutical service partners that specialize in offering an expert, streamlined, and personalized approach.
Trends in Clinical Trial Supply
Handling clinical trial supply involves the careful management of the entire life cycle of investigational drug products used in clinical trials. Encompassing a wide range of activities — including forecasting and planning, procurement, manufacturing, packaging, labeling, storage, distribution, and tracking — clinical trials are inherently complex. Ensuring the investigational drug is available at the right quantity, time and location often involves nimble coordination between various stakeholders. These can include drug sponsors, contract research organizations (CROs), clinical site,s, and manufacturers. Without effective clinical trial supply management, the success of the trial and the safety of the participants can be at risk.
In the past few years, the complexity of clinical trials has been further exacerbated by several key trends:
Constantly evolving regulations
Patient safety depends on the delivery of investigational drug products following a myriad of regulatory factors designed to protect against potential risks such as contamination or misadministration.
However, clinical trial regulatory requirements are constantly evolving with new models for trial administration in different clinical settings. This can be seen in the new regulatory framework set out by the Medicines and Healthcare Products Regulatory Agency (MHRA) in 2023, representing the biggest overhaul in UK clinical trial regulation in over 20 years.1 The U.S. Food and Drug Administration (FDA) also announced measures to modernize clinical trials, with updated recommendations for good clinical practices, in 2023.2
While many clinical trials are conducted in single countries, for drug developers looking to tailor their trial programs or run parallel trials, it is critical to have an awareness of different regulatory regimes in several countries, adding further complexity.
Demand for speed
There is an increasing expectation and demand for a faster drug development process, to progress drug candidates more rapidly through clinical trials and into commercialization. This is driven by pressure from investors to see a return on investment, developers needing therapies to beat potential competitor products, and, of course, the need for patients to receive treatment options as quickly as possible, to minimize the impact of disease. Meeting this demand for accelerated timelines must not come at the expense of efficacy or safety.
Technological advances are offering opportunities to streamline timelines, particularly when working with a new molecule or formulation. Improvements in the sensitivity, selectivity, and efficiency of instruments are helping to advance analytical techniques and allowing developers to rapidly generate data that can inform decision-making. Analytical, research, and development teams must therefore remain informed and adaptable to innovation to remain competitive.
Pressure created by AI-driven drug discovery
As we know, drug discovery and development is a cost-intensive and time-consuming process. Despite the significant investment of time and money, only 10% of drug candidates will succeed from phase I through to commercialization.3
The advent of artificial intelligence (AI) and machine learning (ML) has the potential to revolutionize drug discovery, enhancing predictive modeling, accelerating the screening process, and enabling the integration of data sources like genomics, proteomics,,s and clinical data.4 As a result, the global AI in drug discovery market size, valued at $1.1 billion in 2022, is anticipated to grow at a compound annual growth rate (CAGR) of 29.6% between 2023 and 2024.5
Driven by the rise in AI-supported drug discovery, the industry is likely to be inundated with new drug substances. However, innovations bring new challenges. Each unique compound will require analytical due diligence to suitably verify its safety, purity, and efficacy. Drug developers need to leverage advanced technologies, techniques, and strategies to be able to formulate, develop,p and launch new therapies faster than potential competitors.
With increasing pressure on drug developers to de-risk and streamline formulation, manufacturing, and analytical testing, it is no surprise that partnering with contract development organizations with formulation and testing expertise across a wide variety of compounds is a compelling proposition to pharma and biotech.
Minimizing Risk in Analytical Testing and Formulation Services
Regulatory agencies like the FDA require extensive analytical data during drug review and approval. To provide comprehensive submissions to regulatory bodies and for a drug to gain approval to market, accurate and reliable analytical testing is essential. Any deficiencies in analytical data can lead to drug application delays or rejections.
Having a risk-limiting approach to analytical testing and formulation is also important when considering the data gathered throughout these processes is critical to guiding decision-making, particularly when working with a new molecule or formulation.
Leveraging advanced analytical techniques and technologies that are more sensitive, selective, and efficient can quickly help to generate data, building the right testing program for each Investigational New Drug (IND). This will require contract development and manufacturing organization (CDMO) partners to follow several steps while keeping the end goal in mind:
1. Determine the focus of the testing program.
It is crucial to understand the specific objectives of the investigational drug, such as whether it is intended for upcoming clinical trials following IND application, alternate formulation development, non-clinical research, or something else entirely. Defining the scope of the study as soon as possible allows the R&D team to tailor their testing approach and minimize the time it takes to generate data.
2. Identify the characteristics that define the product’s quality, safety, and efficacy.
Critical quality attributes (CQAs) should align with the product’s purity, potency, stability, bioavailability, and other relevant parameters. Each CQA will require a test to be developed and validated before batch release. Additionally, each functional excipient should have a qualified test to quantify it and generate the data needed to establish relevant specifications.
3. Determine the desired manufacturing process.
Formulation development will provide a thorough understanding of the finished product’s release properties. With an understanding of these properties, it is possible to work backward from the desired outcome to reverse engineer a manufacturing process that achieves the desired effect.
4. Understand the applicable regulatory guidelines.
Depending on the intended use and location of the IND, different regulatory guidelines may apply. Following these guidelines at program initiation is important for efficient development.
5. Consider all available analytical technologies.
Time spent on development is difficult to regain. Investing in the best technologies for the product can offer significant time savings over legacy analytical techniques.
6. Determine the appropriate number of samples and testing frequency.
It is important to establish the sample size and testing regimen using statistical considerations and stability study requirements with the assumption that testing requirements could change as a result of regulatory review.
7. Determine shelf-life and storage recommendations.
Few markets will tolerate a short shelf life. As well as collaborating with technical, sales, and marketing personnel, stability data will be crucial for determining shelf-life and storage recommendations.
8. Consider available funding.
It is critical to balance the need for comprehensive testing with the practical constraints of budget allocation. There must be a focus on a scope of work that ensures all efforts add value.
9. Set clear timelines and milestones.
When working with an outsourcing partner, it is important to communicate timelines and milestones to ensure testing progresses as planned and aligns with the overall drug development timeline.
De-Risking Trials With All-In Provision
As well as following the above steps to de-risk analytical testing and formulation, drug developers should also consider other approaches that could reduce risks, including assessing their outsourcing strategy.
Outsourcing partners providing an integrated range of logistical and administrative support services can ensure greater transparency, reliability, accountability, and flexibility. By supporting from comparator sourcing to manufacturing and analytical release testing, primary and secondary packaging, cold chain storage, Qualified Person release, and robust distribution to multi-site clinical trials or even direct-to-patient, these partners can provide greater security and auditability of compound handling. Additionally, a more centralized approach can provide fewer opportunities for point failures in the supply chain to disrupt the effective administration of trials, as well as more rigorous and better-documented adherence to regulations.
When outsourcing analytical testing and formulation for clinical projects, relying on a partner offering analytical testing, formulation,n, and manufacturing services from the same site can facilitate real-time monitoring, control, and rapid adjustments to help ensure consistent product quality. With on-site analytical services, outsourcing partners can also reduce turnaround time, streamlining process development, scale-up, and routine quality control. Other benefits include improved confidentiality, faster decision-making and collaboration, and cost efficiency.
Looking to the Future of Clinical Trial Supply
Drug developers can anticipate further challenges to arise, caused by emerging trends that will impact clinical trial supply. The move toward digitalization in healthcare is a growing trend driven by the need for efficient and effective healthcare delivery, with pharmaceutical companies increasingly adopting digital solutions to improve their operations and stay competitive. Digital transformation is rapidly going from a “nice-to-have” to a “must-have.”
However, there is a common false assumption that can lead to issues when approaching digitalization: focusing on the technology and not the process it is trying to improve. To gain the benefits that systems managing analytical data offer, it will be important for biopharma’s leadership to integrate these technologies into processes thoughtfully with process improvement in mind.
As part of the digital transformation, AI and AI analytics are poised to reshape R&D, marketing, and supply chain management. Harnessing their potential relies on robust privacy and security frameworks, both of which are essential for fostering a data-driven culture. While digital solutions hold the promise of economic gains, impulsive investments without appropriate infrastructure can cause project failures and financial losses. To drive successful digital transformation, addressing critical challenges including safeguarding patient data privacy, upskilling employees to transition away from legacy systems, and upholding ongoing regulatory compliance is imperative.
In response to the need for streamlined operations and a focus on emerging markets, biologics, and specialty therapies, the pharmaceutical industry is projected to operate on leaner budgets. This shift has led to a notable increase in outsourcing, with digital drug companies relying heavily on CDMOs. Therefore, it has become imperative for the industry to address and rectify any existing workforce gaps in critical skills to effectively navigate the current environment, particularly in development and manufacturing organizations.
Moving forward, drug developers must therefore prioritize strategies that mitigate risks and optimize clinical trial supply management to effectively navigate the substantial industry transformations that lie ahead.
References
- https://www.ema.europa.eu/en/human-regulatory-overview/research-development/ clinical-trials-human-medicines/clinical-trials-regulation
- https://www.fda.gov/news-events/press-announcements/fda-announces-additional-steps modernize-clinical-trials
- Mullard A. Parsing clinical success rates. Nat Rev Drug Discov. 2016 Jun 30;15(7):447.
- Niazi SK. The Coming of Age of AI/ML in Drug Discovery, Development, Clinical Testing, and Manufacturing: The FDA Perspectives. Drug Des Devel Ther. 2023 Sep 6;17:2691-2725. Doi: 10.2147/DDDT.S424991. PMID: 37701048; PMCID: PMC10493153.
- https://www.grandviewresearch.com/industry-analysis/artificial-intelligence-drug discovery-market
Author Details
Robert Feltz, Director of Analytical and Formulation Services- Sharp Clinical
Publication Details
This article appeared in Pharmaceutical Outsourcing: Vol. 25, No.3 July/Aug/Sept 2024Pages: 16-18