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Outsourcing method development offers multiple benefits to companies, including access to experience and expertise, streamlined costs, and development time efficiencies.
The market for outsourced pharmaceutical and biotechnology services is expected to experience healthy growth and is forecast to reach $91.4 billion by 2028 (1). Factors influencing this market swell include rising pressure on drug prices, increasing drug development costs, higher rates of failure, regulatory hurdles, and deficient internal capabilities of sponsor companies, all leading to an increased demand for outsourced solutions (1).
Method development is an evident area where pharma companies can gain an economic benefit from outsourced services, particularly when there are limited to no capabilities for these services in-house. As an integral facet of drug development, optimization and selection of the most appropriate methods can help save on costs and reduce development times.
“The importance of method development cannot be understated,” says Emma Leishman, manager, Advanced Analytics, Avomeen. “Methods are the backbone of being able to answer scientific questions. Advancements in technology, as well as tighter regulatory needs, are driving methods that are more targeted, efficient, and sensitive. Spending time on method development upfront will build a solid foundation for validation and subsequent sample testing.”
“Method development and evolution of a drug product are continuous processes that progress in parallel with one another,” explains Alex Wheeler, senior technician at Wickham Laboratories. “It can be assumed that as the life cycle of a drug product progresses, overall knowledge of the drug product increases as should the robustness of the analytical tests that are being performed.”
Any analytical tests that are due to be performed must relate to the type of drug being developed and are required to comply to any regulatory requirements, continues Wheeler. “During method development, full transparency of the procedure performed is imperative so that when the information is presented to the relevant market authority, it is clear, accurate, and concisely conveys what has been done,” he says. “Investing in robust analytical tests to be established during the method development process will help to ensure that costs are kept down during the further stages of the drug development program.”
Factors for consideration in method development are dependent upon the molecules being developed, agrees Vincent Thibon, technical development lead, RSSL. “For developing methods for small molecules, the analytical method should be developed by looking into the factors such as pH, ionic strength, mobile phase composition, sample preparation, column technology, type of detection, [liquid chromatography–mass spectrometry] LC–MS compatibility, robustness, speed of [quality control] QC, length of time required for stability indication, cost effectiveness, and whether the method is easy to run,” he states. “For developing methods for large, protein-based molecules, the method should be developed by looking into factors such as sample preparation, sensitivity of technique, time to achieve results, complexity of method, and so on.”
A structured method development procedure is vital to ensure the intended methods are fit for the phase of drug product development, they provide the data required for product development support, and they can be validated to the correct product phase following industry guidelines, such as those from the International Council for Harmonisation (ICH), for the release of the product to clinic or market, asserts Amanda Curson, head of Analytical Development, Tredegar, PCI Pharma Services. “The method should be well developed at the start with the view of having a long lifecycle without major changes,” she says. “Redevelopment later can be time consuming and have an impact on regulatory submissions.”
For Jerry Mizell, senior director, Analytical Services, Metrics Contract Services, developing a ‘QC ready’ method is the most critical aspect in the method development process. “Having a method QC ready implies that it is very robust, [and the] rigorous challenging of the method will also establish a stability indication to ensure the quality of API or drug product over time,” he comments.
“Throughout development, methodologies are challenged with stressed and design-of-experiment samples to demonstrate performance. Design space creation is also used to determine the range of chromatographic performance and cover multiple formulation compositions for the product,” Mizell continues. “This approach sets a project up for success if there are future changes to the drug product as the developed method will be suitable for use.”
“Outsourcing method development can give a drug developer access to a more experienced or advanced skill base with minimal delay than it is able to access internally,” highlights Anders Mörtberg, analytical chemist at Recipharm. “As a dedicated specialist in method development, the outsourcing partner can provide dedicated expertise to deliver a much higher quality service than a developer may be able to achieve alone.”
It is fundamental that an outsourcing partner has solid insight into regulatory guidelines and expectations, in addition to being able to provide access to industry-standard separation equipment, Mörtberg notes. “Access to structure elucidation techniques for impurity identification is also advisable in an outsourced partner, as this is often necessary in method development,” he states. “Resources to provide computer-aided method development is desirable, as this can help the partner provide guidance on reducing labor and laboratory costs for method development.”
The three ‘E’s’—equipment, experience, and expertise—are important aspects for consideration when seeking an outsourcing partner for method development services, confirms Leishman. “Equipment should be up-to-date and able to meet dynamic regulatory needs. A wide range of equipment is a plus, since the most suitable instrumentation can be applied, and many methods can be developed at the same time,” she says. “Experience of the company and their scientists is a strong indicator of future success. Ideally, the company has experience with similar analytes and matrixes. Aside from the scientific experience, having regulatory experience with method development and validation minimizes risk.”
Choosing an outsourcing partner with a broad range of expertise, which is somewhat dependent on experience, and scientists on staff who are subject matter experts is advisable, Leishman continues. “Method development sometimes requires a creative approach, [therefore] adequate expertise can ensure that even the most challenging methods are successfully developed in a timely manner,” she emphasizes.
A desirable outsourcing partner should be able to offer a range of modern, but widely available equipment and should have an experienced technical team with vast method development experience and knowledge, concurs
Rebecca Coutts, general manager, Tredegar, PCI Pharma Services. “A company can benefit by working with an outsourced services team that has in-depth knowledge and experience with a range of dosage forms, particularly with dosage forms that can sometimes prove to be more troublesome for method development, such as ointments, creams, suspensions, or very low-dose potent products,” she says. “Using an outsourcing lab that has previous experience on method development, validation, and quality assurance specialist support will ensure the client is guided through the process required to ensure the method is ready for use to release clinical product, and for stability testing.”
For Mizell, development experience represents the most critical capability of a potential outsourcing partner. “Development chemists are not created overnight as it is a learning process that takes time—and there’s no substitute for that,” he asserts. “Knowledge is built upon with every successful development project, especially where technical challenges must be overcome.”
In terms of instrumentation capabilities, Mizell agrees that an outsourcing partner with multiple means of detections in-house, such as diode array, ultraviolet–visible, charged aerosol detection, and LC–MS, are beneficial. “Environmental chambers are also great to have for stressed studies,” he adds.
“Some outsourcing partners can also provide training programs to assist in clients’ learning of regulatory requirements, which would be particularly useful to smaller start-up companies,” confirms Thibon.
Oftentimes, contract research organizations (CROs) are employed for method development due to the wealth of knowledge they can offer in specific aspects of analytical tests relevant to the drug development and approval process, comments Wheeler. “An established CRO will operate facilities that are purpose built for analytical testing, maintained to a high standard, often utilize the most cutting-edge technologies, and already have validated and compliant in-house procedures,” he says.
Whether a single provider or multiple providers of outsourced services are used is dependent on the project and its specific requirements, specifies Curson. “For example, it may be possible for most of the method development to be carried out by one provider; however, there may be individual specialized analysis required, such as X-Ray powder diffraction, particle size analysis or Franz cell analysis, which is more unique and may require a specialized provider to perform method development for one aspect of the analysis,” she explains.
It is beneficial to choose a main provider of services—one that can perform the majority of the method development and validation and outsource any specialized aspects of the analysis to a partner laboratory when required—adds Curson. “The main provider would have overall responsibility for the project requirements with one or two outsourced specialized aspects undertaken by a lab with more specific specialized technical experience or available equipment required for the individual analysis,” she says.
According to Thibon, a clear advantage of using a single provider is the fact that all communication between the client and provider can be streamlined, which can mean that a good relationship can be built. “If using multiple providers, then the key thing is that all providers communicate clearly and on time and are willing to collaborate to achieve the goal,” he notes. “Regulations ensure that methods are consistent across providers, but using a single provider for all method development requirements could introduce efficiencies and reduce costs overall.”
“Using multiple providers will add complexity and may result in reduced efficiency due to coordination losses,” stresses Mörtberg, who highly recommends opting for a single supplier that is capable of providing all required resources for a project, wherever possible.
A single point of contact is undoubtedly advantageous, as it can allow for easier access to the specific project manager at the CRO, timelines are generally clearer and more consistent, and all the information is presented in the same style, concurs Wheeler. “However, there are some risks as well such as the potential for a greater impact on the stages/phases of testing if an issue should arise,” he says.
“By using multiple providers, it could be possible for multiple aspects and stages of testing to be performed concurrently if working with strict timelines, but this would generally require more internal coordination on the part of the client in such cases,” states Wheeler.
“A different approach is to use one provider to coordinate a multi-site study, therefore coordinating all testing, tracking of timelines, and compilation of results,” continues Louise Rigden, technical documentation officer at Wickham Laboratories. “This [approach] means the client still only deals with one point of contact for any information required and results can be reported in a consistent fashion.”
If a single provider has all the necessary equipment and expertise, then that approach can be ideal for a client, comments Leishman. There are time and cost efficiencies that can be gained through the use of a single provider, such as employing one sample preparation technique for multiple methods or employing a singular outsourcing lab to do an entire stability program, and in some instances, volume discounts for work can be applied, she adds.
“By reducing the number of outsourcing partners, a stronger relationship can be established with the single provider,” Leishman says. “However, a niche application or a method that needs a state-of-the-art instrument may benefit from a specialist provider.”
Mizell believes that selecting a single contract development and manufacturing organization (CDMO) that can provide all the required development needs provides a multitude of benefits. Not only does it ensure effective communication between the client and provider but can also lead to reduced meeting frequency and eliminates the need to ship API and/or drug product from site to site for different development activities, he asserts.
“When working with a single CDMO that a sponsor has established a working partnership with, they can have greater confidence that the development being performed will meet all project requirements and timelines,” Mizell summarizes.
1. Grand View Research, Biotechnology and Pharmaceutical Services Outsourcing Market Size, Share, and Trends Analysis Report by Service (Consulting, Regulatory Affairs), by End-Use (Pharma, Biotech), and Segment Forecasts, 2021–2028, Market Research Report (February 2021).
Felicity Thomas is the European editor for BioPharm International.
Vol. 34, No. 6
When referring to this article, please cite it as F. Thomas, “Developing a Method for Success through Partnerships,” BioPharm International 34 (6) 2021.