Blog
November 1, 2021

Patient data – unique challenges, critical uses in the cell therapy value chain

The previous two blog posts in this series provided an overview of why patient-related data matters in cell therapy and gene therapy (CGTs), and how this data enables some of the key stakeholders in the advanced therapy value chain. This installment looks in more detail at key drivers of the CGT value chain, how patient/donor data enables those aspects of the value chain,  and some of the related challenges faced by the advanced therapies sector.

CMC: the patient/donor data, and the critical information it generates, is required by regulators for filings and clinical trials.1,2 An important part of this is building a robust CMC section for BLA filings. Regulatory filings must demonstrate that an efficacious product can be made consistently and meet quality parameters. High volumes of individual patient and aggregate data are generated and must be synthesized to demonstrate an in control process that meets product quality and efficacy requirements, and the underlying data must be readily available and accessible by regulators.1

Read our recent whitepaper, “CMC obstacles in CGT: Four solutions to solve six challenges” to learn more.

Title: Chemistry, Manufacturing, and Controls (CMC) has heightened importance in CGTs
Subtitle: The nature of CGT products makes demonstrating a safe, consistent, high-quality product difficult, especially with limited data. Patient/donor data — individually and in aggregate — is foundational to developing a robust CMC package.
[Refernce 1]
Title: Chemistry, Manufacturing, and Controls (CMC) has heightened importance in CGTs
Subtitle: The nature of CGT products makes demonstrating a safe, consistent, high-quality product difficult, especially with limited data. Patient/donor data — individually and in aggregate — is foundational to developing a robust CMC package.
[Reference 3]
Title: Chemistry, Manufacturing, and Controls (CMC) has heightened importance in CGTs
Subtitle: The nature of CGT products makes demonstrating a safe, consistent, high-quality product difficult, especially with limited data. Patient/donor data — individually and in aggregate — is foundational to developing a robust CMC package.
[Reference 1]

Chain of Identity and Chain of Custody: meeting the stringent regulatory requirements for traceability and lot genealogy is more difficult and complicated for CGTs than for traditional and biologic drug products. Maintaining a complete record of the drug product lot genealogy, which includes the Chain of Identity (COI) and Chain of Custody (COC), is a basic, key aspect of GMP compliance for ALL drugs.4 However, in advanced therapies, more detailed and unique data points are needed relating to the end-to-end donor/patient and product journeys that are not needed in the supply chain of other products. COI and COC are the throughlines that need to be generated and maintained, from patient ordering through treatment. Maintaining these chains provides precise traceability for all of the unique aspects of the supply chain such as the inherently variable raw material of live human cells, the 100+ touchpoints of the process, and the critical workflows and transitions that happen outside the walls of the GMP manufacturing facility. And most importantly, patient safety and treatment efficacy — which rely on the right patient receiving the right treatment at the right time — depends on rock-solid COI and COC. 

Title: Chain of identity (COI) and Chain of Custody (COC) defined rely on donor and patient data
Subtitle: Details about the who, what, when, where, and how for the patient and product journey must be connected to provide a complete picture and ensure patient safety.
Title: Traceability is a fundamental regulatory requirement and critical for patient safety
Subtitle: The FDA and EMA both require rock-solid traceability from the outset. The underlying data is critical for patient safety and orchestrating the patient and product journeys. It ensures that patients get the right treatment at the right time.
[Reference 1]

Title: Traceability is a fundamental regulatory requirement and critical for patient safety
Subtitle: The FDA and EMA both require rock-solid traceability from the outset. The underlying data is critical for patient safety and orchestrating the patient and product journeys. It ensures that patients get the right treatment at the right time.
[Reference 5]
Title: Traceability is a fundamental regulatory requirement and critical for patient safety
Subtitle: The FDA and EMA both require rock-solid traceability from the outset. The underlying data is critical for patient safety and orchestrating the patient and product journeys. It ensures that patients get the right treatment at the right time.
[Reference 6]
Title: Traceability is a fundamental regulatory requirement and critical for patient safety
Subtitle: The FDA and EMA both require rock-solid traceability from the outset. The underlying data is critical for patient safety and orchestrating the patient and product journeys. It ensures that patients get the right treatment at the right time.
[Reference 4]

Data retention: the timeline for using donor/patient data is extended in CGTs and requires careful curation, storage, and accessibility of the information. The initial patient identification and drug product development and production processes are only the start of data’s integral role in advanced therapies and the many information systems that will be accessed. Historical data related to patients/donors, products, and processes is used for both patient related purposes and product and process knowledge and improvement purposes.2,5,7

Title: Regulators expect data — and traceability — to be accessible into the future
Subtitle: Long-term follow up requirements and potential future adverse health events have prompted regulators to require patient/donor to be accessible well into the future that traceability is maintained.
[Reference 5]

Long-term follow up: HCPs and payers will use Electronic Medical Records (EMRs) and Electronic Health Records (EHRs) for activities related to a specific patient and treatment such as evaluating patients for a therapy, verifying benefits, treating the patient, and reimbursing providers. Post treatment, advanced therapy patients must be carefully monitored for health outcomes due to the many unknowns with therapies based on modified human cells and genes.7 Look forward, look back, a link which is established between donors and patients at the inception of the product journey must be maintained to investigate and understand the underlying causes of serious health issues that a donor or patient may develop years after treatment. Additionally, as the industry evolves and expands, patient data can be used as real world data (RWD) and generate real world evidence (RWE) for clinical trials, approvals, and label expansions.8 RWD and RWE are increasingly important for label expansions and drug approvals, with 48% of drug approvals in 2019 including some RWD or RWE and 75% of approvals in 2020 utilizing RWD or RWE.9 Patient identifiers, such as a unique COI identifier, can be used to facilitate curation of patient/donor specific information across systems and verify the validity of information.

Process and product optimization: improvements to the product and process — and changes to the supply chain — may be needed over time. This could arise from scaling out across geographies to new manufacturing facilities and collection facilities or making process changes based on learnings from the development process and commercial production. In advanced therapies, patient/donor data is a critical component of the data set needed to inform product and process knowledge and to revise regulatory filings in both the short and the long term.2

Title: Improving patient, product, and process knowledge with patient/donor data
Subtitle: Data captured along the end-to-end supply chain — tied together with a solid COI — enables the ability to analyze and gain critical insights into aspects of CMC that can be used for improving the patient and product journey and regulatory filings.
[Reference 2]

The patient/donor are the process and the product in advanced therapies, creating a value chain where the patient/donor data has significant, critical value. This data is collected, stored, and utilized by a wide range of stakeholders and systems (EMR, CRM, ERP, MES, HUB, etc.) and is necessary to meet regulatory requirements, develop better therapies, and provide access to patients. Today that is a challenging proposition due to data quality and accessibility issues.

Next, the fourth and final blog in this series will turn to the future and offer solutions to these challenges.

Blog #1 – Patient data – the unique role in cell and gene therapies (CGTs)
Blog #2 – Patient data – why it is critical for cell and gene
Blog #4 – Integrated patient data – the future of advanced therapies

References:

  1. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs): Guidance for Industry. Silver Spring, MD. The FDA. January 2020.: https://www.fda.gov/media/113760/download
  2. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved Application: Certain Biological Products: Guidance for Industry. Silver Spring, MD. The FDA. June 2021.: https://www.fda.gov/media/109615/download
  3. Dunn, Andrew. Unblinded: Scott Gottlieb on Biosimilars’ Precarious Moment and the Gene Therapy Boom. BioPharma Dive. March 2019.: https://www.biopharmadive.com/news/unblinded-fda-scott-gottlieb-biosimilars-gene-therapy/549997/
  4. Current Good Manufacturing Practice for Finished Pharmaceuticals, 21 CFR Part 211, Sec 211.188 Batch production and control records. 2018.: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=211.188 
  5. European Commission, EudraLex. The Rules Governing Medicinal Products in the European Union, Volume 4, Good Manufacturing Practice: Guidelines on Good Manufacturing Practice Specific to Advanced Therapy Medicinal Products. London, UK. The European Commission. November 2017.: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf 
  6. Human Cells, Tissues, and Cellular and Tissue-based Products: Current Good Tissue Practices, 21 C.F.R Part 1271 Subpart D Section 1271.90 Tracking. 2020.: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=1271.290
  7. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. Long Term Follow-Up After Administration of Human Gene Therapy Products: Guidance for Industry. Silver Spring, MD. The FDA. January 2020.: https://www.fda.gov/media/113768/download
  8. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Oncology Center of Excellence (OCE). Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products: Guidance for Industry. Silver Spring, MD. The FDA. September 2021.: https://www.fda.gov/media/152503/download
  9. Brennan, Zachary. How to collect and submit RWD to win approval for a new drug indication: FDA spells it out in a long-awaited guidance. EndPoints News. October 2021.: https://endpts.com/how-to-collect-and-submit-rwd-to-win-approval-for-a-new-drug-indication-fda-spells-it-out-in-a-long-awaited-guidance/