A lateral flow assay design & development pathway under an ISO certified process explained.

Introduction
Key Phases Throughout a Certified Lateral Flow Development Pathway
Project Set Up: Laying the Foundation
Proof of Concept
Optimisation
Scale up & Pilot batch
Technical Transfer
Key Takeaways

Introduction

Developing a lateral flow assay can be complicated and a development project requires the appropriate design control processes and pathway to ensure you are developing the right product, for the right market.  Additionally, establishing performance requirements early in the design process enables design for and a robust product in routine manufacture. In this blog Abingdon Health’s CTO, Nina Garrett, explains what that process looks like under an ISO certified Quality Management System.

Abingdon Health’s team has over 20 years’ experience in the lateral flow market and is a knowledge leader in the development, scale-up, transfer, manufacturing and regulatory approval of lateral flow products across a range of sectors. If you would like to understand more about the development, technical transfer, manufacturing and regulatory process and discuss any specific requirements don’t hesitate to contact Abingdon’s highly experienced team.

Key Phases Throughout a Certified Lateral Flow Development Pathway

Lateral Flow Tests (LFTs), or Lateral Flow Immunoassays (LFIAs), are increasingly becoming a go-to format for rapid diagnostics, offering user-friendly and near-instantaneous results. Before these tests reach the point of commercialisation, they undergo a rigorous design and development process to ensure what is released to the market, be it clinical or at-home (over the counter), animal health, environmental or food safety settings to name same of the industries, has achieved required performance accuracy and reliability. This blog takes a look at the key phases of a certified lateral flow development pathway, guiding you through the journey of transforming an idea into a dependable diagnostic tool.

Project Set-up: Laying the Foundation

The initial phase is one of the most important where the foundation is laid out for the entire design and development process. Here, project and product goals are clearly defined, including the target analyte (the substance being detected), desired sensitivity and specificity, and regulatory requirements. A detailed project plan is established, outlining timelines, resource allocation, and potential risks. A contract research organization (CRO), like Abingdon Health, will always ensure adherence to quality standards which is why using a CRO with a certified Quality Management System (QMS) can be the difference between a successful development for market access (see our blog on Design & Develop for Success: Why R&D and Regulatory go hand-in-hand to learn more) and routine manufacture.

Key documents within this phase:

• • Commercial Product Requirements (CPR) – outlines early technical and regulatory requirements.
  • Product Requirement Specifications (PRS) – The PRS is the defining control document to guide the development.
  • Design & Development Plan (DDP) – This maps the pathway, guided by the PRS, to ensure inputs are meeting desired outputs.

Proof of Concept (POC): From Theory to Prototype

This exciting phase translates theoretical concepts into tangible prototypes and is where the majority of risk lies within any development project. Working with an accomplished CRO helps mitigate risk and can be the difference in success or failure.

Within POC, capture and detection antibodies specific to the target analyte are researched and evaluated. Conjugation techniques are employed to link these antibodies with reporter molecules, like gold nanoparticles, which generate a visual signal upon binding. Crucially, the assay format and components, such as the nitrocellulose membrane, conjugate and sample pads, are also selected. The success of this phase hinges on demonstrating the feasibility of the LFT design in detecting the target analyte in the final sample matrix.

Key objectives within this phase:

• • Reagent and component selection (test line, control line and conjugate reagents).
  • Test strip format agreed.
  • Prototype performance understood and agreed for next stage.
  • Small prototype batch provided for testing.

Optimisation

Now that we are through the exciting, yet challenging, POC phase the focus turns to optimising what has been developed thus far to ensure key parameters such as the sensitivity, specificity are met. Beyond this, a limited stability study is initiated, and the Quality Control (QC) panel (to learn more on QC panels, read our blog: Choosing the Right Quality Control Panel ) specifications are agreed.

The limited stability study gives you early confidence that your product will remain stable under temperature-controlled environments in the formal stability studies which are required for the performance of the product and setting the expiry date.

Having a well characterised QC panel is critical for the life cycle of your product to ensure every batch meets the same exacting standards throughout the later development, transfer and manufacturing stages.

Ultimately, optimisation drives confirmation of performance of the LFT and get us to a stage where we are planning to transfer the assay to manufacture.

Key objectives within this phase:

• • Final adjustments to formulas completed
  • Informal stability study initiated on prototypes
  • Transfer to Production Plan
  • Target QC specifications defined.

Scale up & Pilot Batch: Bridging the Gap to production

With a promising prototype in hand, the focus shifts towards scalability. Processes established during optimisation are translated into large-scale manufacturing protocols. Here, the focus is to ensure consistency and efficiency in production while maintaining test performance. A critical step involves producing a pilot batch – a small-scale production run using draft manufacturing documentation – to validate the scalability of the manufacturing process. The pilot batch undergoes rigorous testing to confirm that the LFTs maintain performance when produced in larger quantities. A core mantra within this phase is ‘we’ve built it, now can we break it’. Provided we can’t, we know we have a robust and quality product.

Key objectives within this phase:

• • Draft Failure Mode Effect Analysis (FMEA).
  • Define Bill of Materials (BOM) & Cost of Goods Sold (COGS).
  • Draft manufacturing & QC documentation.
  • Pilot Batch devices manufactured to verify the manufacturing and QC process.
  • Process Design Freeze

Technical Transfer: Gearing Up for Production

The final phase through the certified design and development pathway involves transferring the optimized and scaled LFT design and manufacturing processes into large scale batch manufacture. Finalised manufacturing documentation is used outlining procedures, quality control measures, and acceptance criteria. The manufacturing teams undergo training and produce the LFTs according to the established protocols. Where possible, lot-to-lot diversity is introduced into the batches from the supply chain to ensure the processes are robust and can handle expected lot diversity.

The batches manufactured are used for performance evaluation work that includes both analytical studies and clinical (where necessary) studies. Abingdon’s end-to-end regulatory support services runs in parallel with this process and continues after the batch production to gain your market approval.

The technical transfer phase paves the way for full-scale routine production of the lateral flow test and provide formal batches to use to gain access to your target markets.

Key objectives within this phase:

• • Three Validation Batches (VB) manufactured under formal manufacturing and QC conditions using automated or manual primary and secondary assembly equipment (process is dependent on expected routine batch sizes).
  • VB’s available for use in performance evaluation.
  • Lot-to-lot diversity introduced for robust process validation.
  • Routine production batch size established.
  • QC Panel and specifications confirmed.

Key Takeaways

Successfully navigating each of these key phases is a challenging yet ultimately rewarding process. Entrusting your project to an expert full-service provider who design and develops with in-house manufacturing abilities in-mind, can take a promising concept and transform it into a reliable and readily available diagnostic tool. The journey from project set-up to technical transfer and regulatory approval requires meticulous planning, scientific expertise, and rigorous quality control. This ensures that the resulting LFTs deliver accurate and dependable results, empowering healthcare professionals and individuals alike.

Decades of experience in the development of LFAs at Abingdon Health, taking them from concept to commercialisation, has us well placed to develop your lateral flow test ensuring that the materials selected are appropriate for your test and allows you your desired end-product. We have established effective processes that ensures efficient and cost-effective development, technical transfer and scale-up of LFAs. Abingdon is ISO 9001 and ISO 13485 certified and adheres to Good Manufacturing Practice. This framework ensures that developed tests are manufactured in a consistent and robust manner batch in, batch out. Contact the Abingdon Team  via the form below to see how we can help take your test from R&D into reliable manufacture and commercial success. Also, discuss our value-added services such as regulatory and commercial support that provides a de-risked and streamlined route to market.