Submitted: August 12 2015 Published: September 15 2015; 

Steps to product

The first section covers the various meetings required by FDA in preparation for an investigational new drug (IND) application, including what those meetings will entail, specific details on timings and logistics, and briefing document requirements (Figure 1The ‘Steps to Product’ section within the US Cell Therapy Regulatory Toolkit, which covers the meetings required by FDA in preparation for an investigational new drug (IND) application.). Information on the IND application itself and how the content is normally organised is also covered, and users can complete a simple questionnaire in order to determine how FDA will categorize their product (note the final ‘Resources’ section in the toolkit briefly details the specific Code of Federal Regulations [CFR] that apply to the IND application process.) There are also descriptions of the meetings that occur with FDA when Phase I and Phase II trials are completed, and details on the process for submitting a biologic license application (BLA), including a timeline for all the activities that occur during the BLA process.

Manufacturing

The second section looks at the manufacturing requirements for each stage of product development from preclinical development up to commercialization (Figure 2The ‘Manufacturing’ section, which covers the manufacturing-related requirements for each stage of product development.). It includes information on the timeline about when finalised potency assays are required, as well as the timeline for when compliance with current good manufacturing practice (cGMP) is necessary. Ensuring these elements are in place by the correct timepoints minimizes unnecessary delays in achieving the official approval to proceed with commercializing the product.

Expedited Programs

The third section details the various expedited programmes available to those developing cell therapies in the US (Figure 3The ‘Expedited Programs’ section, which details the various alternative regulatory pathways available to those developing cell therapies in the USA.). Fast Track Designation, Breakthrough Therapy Designation, Orphan Status, Humanitarian Use Device Designation, and Accelerated Approval can be requested at any time during the development cycle. Special Protocol Assessment is usually requested at the end of Phase II clinical trials, whilst Priority Review Designation is requested when the BLA is filed. For each programme, information is included that covers qualifying criteria for the product to fit the specific programme, when to submit the request for accessing the programme, and the timelines for FDA response. The corresponding benefits that ensue from joining the programme are also listed. For example, the developers of products that are able to acquire Orphan Status may take advantage of a number of benefits, including 7 years of market exclusivity, certain tax credits, and the waiving of certain fees.

Conclusion

The information contained within the US Cell Therapy Regulatory Toolkit provides accessible regulatory education to users about specific requirements they can expect during product and clinical development in the USA. Users are welcome to navigate the pages, and use it as a starting point in seeking to understand the regulatory pathway for taking cell therapies into the clinic.

Endnote

The toolkit was constructed using information available in 2014. It is inevitable that regulatory requirements will change over time, and looking ahead, users should therefore check whether there have been any subsequent changes introduced by the relevant regulatory bodies.

Acknowledgements

The authors are grateful to Karen Rowland for design and creative concept for the toolkit.

Financial & competing interests disclosure

The Cell Therapy Regulatory Toolkit was developed within the British Regen Industry Tool Set (BRITS) project (2010–2014) funded by Innovate UK (then the Technology Strategy Board) under their Regenerative Medicine Program: Value Systems and Business Modelling. C Mason was the Principle Investigator and EJ Culme-Seymour was an investigator on the project.

This work is licensed under a Creative Commons Attribution- NonCommercial – NoDerivatives 4.0 International License.

Affiliations

Emily Culme-Seymour
Director, London Regenerative Medicine Network, 2 Royal College Street, London NW1 0NH, UK

James Lawford Davies
Hempsons, Hempsons House, 40 Villiers Street, London WC2N 6NJ, UK

Julian Hitchcock
Denoon Legal, 14a Clerkenwell Green, London EC1R 0DP, UK

Julian Mason
Faculty of Science, Engineering and Computing, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK

Melissa K Carpenter
Carpenter Group Consulting Inc., Washington, USA

Chris Mason
Professor of Regenerative Medicine Bioprocessing, Advanced Centre for Biochemical Engineering, University College London, Bernard Katz Building, Gordon Street, London WC1H 0AH, UK