An Interview With Amanda Blackwell - Head of Analytical Development, PCI Pharma Services Tredegar.

Analytical Method Development in a High-Potent Facility

Analytical method development is a cornerstone of pharmaceutical outsourcing. In this Q&A, Amanda Blackwell—Head of Analytical Development at PCI Pharma Services’ high potent manufacturing facility in Wales, UK—outlines the discipline’s key considerations, shedding light on why it is so vital to successful drug development.

What are the key elements of analytical method development, and why is it important to get it right?

Understanding the development objective, and gathering relevant data, is fundamental. For example, should the method be suitable for analysis of the Drug Substance (DS) initially, with the potential to develop at a later stage for the Drug Product (DP)? And what is the basic chemistry of the DS? Is there existing information that can be utilized, such as known degradation products or other expected peaks of interest, solubility data, pKa, molecular structure, molecular stability, etc.? Searching for existing Pharmacopoeia methods for the DS or similar molecules is a common approach, as adaptation and optimization of any existing methods can reduce overall development timelines.

An Analytical target profile should be prepared to clearly outline the requirements of the method and it is important to establish a structured method development procedure. This is to ensure that methods are fit for purpose, provide the required data for product development support, and enable validation to the correct product phase in accordance with ICH guidelines for release to the clinic or market. Methods should also be stable indicating if they’re to be used to generate stability data for the assignment of shelf life. Additionally, methods should be well-developed from the outset, with a view of having a long lifecycle without any major changes, as redevelopment at a later stage can be costly, time-consuming, and have an impact on regulatory submissions.

What capabilities should a CDMO be able to offer for analytical method development?

It almost goes without saying, but a well-equipped laboratory is essential. This would ideally include different models of HPLC/UPLC systems for method robustness, dissolution apparatus, viscometers, spectrophotometers, Karl Fischer titration equipment, physical testing equipment, balances, and so on. A highly trained analytical technical team with vast experience in method development, with an innate ability to troubleshoot and provide solutions for overcoming any method development issues that may arise, is another must-have.

An experienced team, working with modern equipment, in an industry-leading CDMO with decades of experience, means that sponsors and clients can be guided through the process in a timely manner, which is especially useful when the CDMO has extensive knowledge of dosage forms that can prove more troublesome— such as ointments, creams, suspensions or low dose, highly potent drug products.

What questions should a sponsor ask of their potential CDMO partner?

Drawing on my previous point, some important questions to ask of your potential CDMO partner in terms of analytical development capabilities are:

• What is their previous practical experience in developing methods for a particular dosage form?
• How many successful validations have they performed within the past 5 years as a result of initial method development?
• What is their available equipment, in terms of make, models, and the number of pieces of equipment available?
• How much available capacity do they have? This would relate to the laboratory’s availability to start work, the resources available for allocation, and an agreement on the project expectations to ensure the CDMO partner is able to deliver— for example if the sponsor wanted summary development reports or copies of raw data.
• Is the CDMO able to safely handle the compound, if it’s highly potent/cytotoxic?

CDMOs that are able and willing to invest in their analytical capabilities are a strong indicator that they are committed to providing end-to-end solutions for their clients, limiting the amount of additional outsourcing that may be required during a drug development lifecycle.

The CDMO partner may ask a series of questions too, prior to on-boarding a new project involving analytical method development. These may include:

• Is there any available data to review in relation to the physical and chemical properties of the DS?
• What information is available on potential dosage form, strength, formulation, and the phase of drug development?
• Is any previous analytical information or methodology available? This can be particularly useful, as a client may require method development for a DP that may already have DS methods available to share (which might include forced degradation data) and this can be utilized to reduce the DP method development timelines.

What regulatory considerations must be taken into account?

Successful method development must produce a method that is fit for purpose and able to be validated according to ICH guidelines. It must be specific, accurate, reproducible, and robust for the analysis of the drug substance or drug product. Additionally, there must be clear, detailed, and structured standard operating procedures (SOPs) relating to both the method validation procedure (again adhering to ICH guidelines), and SOPs for recording and investigating OOE/OOS results obtained during regulatory-compliant method validation.

The criteria set in validation protocols must also follow the relevant regulatory guidelines with approval from Analytical Technical Personnel, Quality Assurance, and ultimately the client. Lastly, clients should consider the CDMO’s previous experience in developing and validating methods for drug products destined for the intended markets, showing experience in successfully adhering to that region’s predominant regulatory authority.

Is it more beneficial to use a single outsourcing partner for outsourced analytical method development?

This depends on the requirements of the individual project. For example, it might be possible for the majority of method development to be carried out by one provider, however, there may be individual specialized analysis required such as XRPD, particle size analysis, or Franz cell analysis, which is more unique and may require the services of a specialized laboratory to perform method development for one particular aspect of the analysis.

Selecting a CDMO partner that is able to perform the majority of the method development and validation activities, and handling any further outsourcing to an approved partner laboratory, can be beneficial. Overseeing every aspect of analytical method development, whilst performing the vast majority in-house, provides clients with a more robust service, which is critical when striving for speed to the clinic, approval, and commercial launch.

Author Details

Amanda Blackwell - Head of Analytical Development, PCI Pharma Services Tredegar

Publication Detail

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