Our Assay Development & Validation team are responsible for the following with respect to CDx Assays

• Assay design via selection of assay components from approved suppliers 
• Establishment of analytical methodologies and associated QC metrics
• Formal product lock achieved under design control and risk management (QSR 820, IVDD/IVDR and ISO13485 & 14971 compliance)
• Engagement with relevant regulatory authority to outline product development plan and obtain feedback to ensure alignment
• The assay’s analytical and clinical validation (performed in compliance with ISO13485, CFR 860.7 and IVDD/IVDR, CLSI guidelines and importantly regulatory feedback obtained via pre-submission process)
• Management of design change
• Feasibility analysis, risk analysis and validation prior to regulatory submissions for approval of design change

All validation is performed under design control and risk management.
All supported by Almac’s Biostatistics team who liaise and work collaboratively with the Assay Development and Validation team to establish the analysis plans, data management flow and reporting for each validation study performed.

Almac’s software development team develop and validate software in compliance with IEC62304 as well as ISO14971 and QSR Part 820.30 and have supported Almac IVD programs.
Almac’s software team have extensive experience of engaging with the FDA to support obtaining IDE approval, pre-submissions and preparation for PMA submissions. Additionally, they are also instrumental in supporting CE-marking of clinical trial assays.
In terms of compliance of software processes, the following FDA guidance documents are complied with:

• General Principles of Software Validation
• Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices
• Off-the-Shelf Software Use in Medical Devices

Almac also perform cybersecurity design and risk management as practices as per the following guidance documents:

• Content of Premarket Submissions for Management of Cybersecurity in Medical Devices
• Cybersecurity for Networked Medical Devices Containing Off-the-Shelf (OTS) Software
• The NIST’s Framework for Improving Critical Infrastructure Cybersecurity

Finally, with respect to data integrity, data analysis and reporting software that is developed and validated will be examined with reference to the Data Integrity and Compliance with Drug CGMP Questions and Answers Guidance to Industry 2018 document. Almac ensure all system data is generated and stored in a manner to conform to ALCOA principles (attributable, legible, contemporaneous, original, accurate).

The manufacturing team have extensive experience of engaging with the FDA to support obtaining IDE approval, pre-submissions and preparation for PMA submissions; additionally, they are also instrumental in supporting CE-marking of clinical trial assays.

Almac have a manufacturing team who have established IVD manufacturing processes which constitute current Good Manufacturing Practice (cGMP), are CFR 820 compliant and have achieved ISO13485 certification. 

These processes result in generation of the necessary evidence to ensure consistent assay component supply, adequate reagent release processes for the validation studies and a robust assay assembly, labeling, release and monitoring process for final commercialization.

Following supplier qualification, all reagent and platform specifications are locked and agreed, and this is documented via execution of Agreements with the relevant manufacturers, with subsequent on-going monitoring of all suppliers against defined criteria. 

Supplier selection and manufacturing plan will follow the guidelines laid out in GHTF/SG3/N17:2008 Quality Management System – Medical Devices- Guidance on the Controls of Products and Services Obtained from Suppliers.

Following selection of components and product lock, the assay system is verified, the assay is then assembled and released by Almac in accordance with ISO13485.

The ability to manufacture the assay in a commercial setting will be assessed via process validation.

Monitoring and surveillance procedures of the assay are developed to ensure continued process verification of the commercial product.

Find out more information on Almac’s CDx Manufacturing Capabilities.