Picking the Perfect Method Development Partner

Pharmaceutical Technology, Pharmaceutical Technology, 2021 Outsourcing Resources Supplement, Volume 2021 Supplement, Issue 3
Pages: 26–29

There are some key questions that should be asked by both the sponsor company and the outsourcing partner before undertaking a method development project.

Outsourcing time-consuming and costly services is becoming increasingly popular within the bio/pharma industry. The right contract development and manufacturing organization (CDMO) can not only provide the best equipment for certain tasks but can also provide a wealth of expertise to provide the best possible chance of success.

To learn more about best practices for selecting an outsourcing partner and the questions that should be posed to a sponsor company when approaching a method development project, Pharmaceutical Technology spoke with a panel of experts. The panel included Emma Leishman, manager, Advanced Analytics, Avomeen; Alex Wheeler, senior technician, and Louise Rigden, technical documentation officer, both from Wickham Laboratories; Rebecca Coutts, general manager, and Amanda Curson, head of Analytical Development, both at PCI Pharma Services; Vincent Thibon, technical development lead, RSSL; Jerry Mizell, senior director, Analytical Services, Metrics Contract Services; and Anders Mörtberg, analytical chemist, Recipharm.

Selecting an outsourcing partner

PharmTech: Could you provide some best practices for selecting the optimal outsourcing partner for method development?

Leishman (Avomeen): Finding an outsourcing partner can be tough—nobody wants to be left hanging on a critical project due to outsourcing delays. A good outsourcing partner will understand this and will do their best to meet your needs. Communication is key. You should be able to talk directly to the scientists and technical directors who will be overseeing the project. That way, the project can get started correctly with everyone on the same page.

When selecting an outsourcing partner, the experience, expertise, and equipment capabilities of the outsourcing lab should be assessed. If the method is for filing with a regulatory authority, then quality systems should be part of the initial assessment. It is especially promising when a partner has prior experience with similar methodology or even recommendations from previous clients.

Wheeler (Wickham Labs): Before contacting a contract research organization (CRO), the company should establish exactly what aspects of the method development can be done in-house and what needs outsourcing. Once it has been established what testing is required, the relevant stakeholders internally should familiarize themselves with the regulatory guidelines of these tests to provide at least a basic understanding of the testing requirements. By having this knowledge, it will make communicating the company’s needs easier and ensure the chosen CRO can offer the best-suited and most robust testing.

When first reaching out to potential partners, important questions to ask are what they can offer you, which tests they have validated and have experience with conducting regularly, and what regulatory certificates they have. For a good manufacturing practice (GMP) product to successfully go to market, it is imperative to ensure that the testing is performed by a GMP accredited CRO.

Also, and possibly most importantly, expectations around timelines should always be discussed before engaging in testing as just because a company can offer the testing does not always mean their availability will match the required timeframes for any given project. A good recommendation is to establish expectations early, communicate clearly, and ensure there is contingency built into your project timeline to deal with any issues that may arise.

Rigden (Wickham Labs): Moreover, the experts in a CRO can advise on regulatory requirements and therefore assist in advising on the testing required as it can sometimes be difficult to interpret the guidelines. Consultancy services can be invaluable to a smaller drug development organization, or to clients such as student researchers who may not have experience of the industry.

Coutts (PCI Pharma Services): Best practices for selecting the best outsourcing partner for method development include picking a partner who has the following: previous practical experience in developing methods for particular dosage forms; a number of successful validations as a result of initial method development over the past five years; available equipment with multiple models, capacity, and resources that will be allocated; the ability to deliver within required timelines; the ability to provide summary development reports or copies of data required to support regulatory submissions; a good history with the regulatory authorities; and lastly, the ability to safely handle certain compounds, for example, potent molecules.

Thibon (RSSL): In addition to the outsourcing partner complying with regulatory standards (e.g., company standards, GMP approvals, quality compliance procedures, and auditing systems), we think that the correct outsourcing partner would ensure that there is good, clear communication and collaboration, and good planning to meet agreed timelines. With these practices, a strong relationship can be built as trust is key.

Key questions to consider when selecting a potential outsourcing partner include: Are the labs approved by the relevant regulatory body (e.g., FDA or Medicines and Healthcare products Regulatory Agency)? What technical knowledge and instrument capabilities are available at the CRO? Can they assist developing all the methods that are required? Can they develop the methods within the required deadlines?

Mizell (Metrics Contract Services): A company should ask for examples of previous development projects and what led to success. Detail should be given regarding the types of samples in which methodology was developed. For example, asking whether a company specializes in method development for inhalation, ointments, creams, liquids, or solid oral dosage formulations is an essential first question. Detail should also be given describing development experience with challenging molecules or formulations and how those challenges were overcome. For the initial meeting with the prospective CDMO, sponsors should interview chemists and ask for the strategies that would be employed when developing methodologies. This could include asking what strategy they use to develop a tablet dissolution procedure where the API is practically water insoluble.

Mörtberg (Recipharm): There are a few key questions that a drug developer should ask of a potential partner before entering a working relationship with them. These questions include do you have experience in similar projects to mine? Do you know what to do, and will your solutions work effectively? What is your track record in successful method development in my particular field or category, such as small molecules, or biopharma? What are your team’s qualifications? How many members of your team have in-depth expertise in my field? Do you have the necessary instrumentation and infrastructure to support me and my project? Do you have a GMP-certified laboratory? When can the work be finished? It is often the case that developers ask when the work can be started, but delivery is the key issue to consider. Are you a reliable and well-established partner that will still be around to be able to deliver the project? How will the method development work be documented? It is important to understand how and why specific method parameter choices were made by a partner. When the new International Council for Harmonisation guideline Q14 on method development will become effective, it is important the outsourcing partner is well versed with its implications for method development practices.

Establishing service requirements

PharmTech: Are there specific questions the outsourcing partner should ask too, before undertaking a potential method development project?

Curson (PCI Pharma Services): Before undertaking a potential method development project, outsourcing partners may want to ask what data [are] available for review on the physical and chemical properties of the drug substance, also whether there is information on potential dosage form, strength, formulation information, and the phase of drug development. Additionally, they may want to ask if there is any previous analytical information or methodology available. For example, a client may require a method developed for the drug product and may already have developed drug substance methods that can be shared to help inform the drug product method development approach.

Mizell (Metrics Contract Services): First, the potential partner should ask is there a technical package for the API or drug product that describes the chemical and physical properties of both? Properties such as morphology, solubility (organic, aqueous, and pH range solvents), stability, and any forced degradation data should be requested along with methodology, and any associated validation reports. Having a solid technical package available when beginning development typically accelerates the development process.

Thibon (RSSL): Questions we try to ask before undertaking potential method development projects include: What are the purposes of the method? How many formulations and are there any plans to extend formulations? When the method is used routinely, will it be used for quality control testing or investigation only? When is the method needed by and have other alternative techniques been considered? Is the method development project to improve an existing method or develop something from scratch?

Mörtberg (Recipharm): There are several questions that a drug developer can expect to hear from a potential partner. Answering these questions as comprehensively as possible is key to help the partner provide a realistic timeframe for delivery and deliver the best possible service. The key questions a drug developer should answer include what is the ‘pre-history’ of the project? Could you provide any background information and context to help understanding of the project’s needs? How do you intend to use the method once it is developed? Any method development project needs to address the actual use of the method to be successful. When does the project need to be delivered in full? Answering ‘as soon as possible’ should be avoided as it will necessarily lead to higher costs. What deliverables do you want to specify? What protocols, reports, or method descriptions do you want to receive on completion of the project?

Wheeler (Wickham Labs): Potential partners should establish the intended use of the product. Knowing this can not only help the potential partner establish testing but could also help deliver valuable insight regarding how the product should be tested, specific quantities to test, and any regulatory specifications. If the CRO has tested similar products before, they may also be aware of additional requirements which had not already been considered, and capturing these issues early on could save time later.

The CRO should be asking questions specifically relating to the product. For instance, if the testing required is microbial limits testing, then it should be established if the product contains properties or constituents which might inhibit microbial growth during the product’s validation.

A timeframe should also be established early on, with the CRO confirming they have the capacity to perform exactly what the client has requested. If those targets cannot be met, it should be considered whether there is room to compromise on the timeline or alternatively, whether new methods or systems could be considered for validation to facilitate the project.

Rigden (Wickham Labs): It is also critical that confidentiality and technical agreements are in place to provide guidelines for the relationship between the parties before any testing commences as this protects the customer and the CRO by establishing responsibilities and ensuring they are meeting regulatory and legal requirements.

Leishman (Avomeen): The purpose of the method must be established to guide the work. A method development scientist will ask questions to figure out the purpose. For example, who will be using this method? What sort of conclusions will be made based on data obtained from the method? Where is the method going to be used? At a single lab or transferred between sites? When will this method need to be implemented? Why is this method required? How has this testing been performed in the past? Does the method need updating to keep up with current standards?

The regulatory requirements and the timeline should be established to scope the work. Timelines to reach the end goal of the method need to be realistic—it is not possible to develop a method from scratch and validate it within a week. Obtaining detailed information on the analyte, the matrix, and the final purpose of the method assists with devising a customized and purpose-driven scope of work.

About the Author

Felicity Thomas is the European editor for Pharmaceutical Technology Group.

Article Details

Pharmaceutical Technology
Supplement: Outsourcing Resources 2021
August 2021
Pages: 26–29

Citation

When referring to this article, please cite it as F. Thomas, “Picking the Perfect Method Development Partner,” Outsourcing Resources 2021 (August 2021).