Audit Readiness For Cell & Gene Therapy Companies
By Susan Shockey, Clarkston Consulting

Cellular and gene therapy (CGT) development areas have been increasingly active, and the approval pipeline for CGT products continues to grow.
CGT products, human gene therapy products, and certain devices related to CGT are regulated by the CBER, while the FDA regulates human cells, tissues, and cellular and tissue-based products (HCT/Ps) under Title 21 of the Code of Federal Regulations (CFR), Part 1271.1 The FDA information page on CGT products2 provides links to numerous guidance documents and CGT regulatory reference information to help CGT companies understand the regulatory environment specific to CGT.
As CGT companies grow and move through the product life cycle, successfully completing a regulatory inspection is a critical step to demonstrating compliance with regulations in order to get approval to start clinical trials or the commercialization of a product.3
The use of audits to qualify a site is a standard part of the traditional quality models for drug products, and the same degree of diligence and preparation is required for CGT companies. Much has been written about how to prepare for a regulatory inspection4 by a health authority, yet most of the literature is geared toward traditional pharma or medical device companies. Let’s look at some of the special considerations that need to be addressed for CGT companies.
Audit Areas
CGT product manufacturing is a uniquely complex process, and companies are required by regulation to qualify sites performing all the steps and methods as part of their manufacturing processes. Regulatory agency and company audits include the standard key areas, such as evaluation of the quality management system, process validation and verification, and a review of the facilities. However, because each step of the CGT process, from cell collection to the delivery of the therapy, involves several processes that bring their own risks and require controls, additional preparation for an audit may be required.
Some of the unique CGT audit areas to be considered include the following:
- Collection Process Control: Auditors will confirm proper preparation and monitoring of the patient and equipment to yield the appropriate quality of raw material during apheresis, bone marrow aspiration, tumor excision, etc. It is important that clear, effective procedures are in place for these processes to ensure the safety of patients and the integrity of the materials collected.
- Raw Materials Control: The raw materials and drug products are sensitive to environmental conditions and may be affected by factors such as time in transit, humidity, temperature, packaging, and handling. The auditors must verify that appropriate procedures and processes are in place5 to ensure CGT materials are handled, packed, and transported in compliance with applicable standards.
- Outsourcing Control: The use of vendors for testing and logistics must be evaluated to ensure that they meet relevant standards. Auditors will need to evaluate the vendor selection processes to ensure only qualified vendors are used. There should also be periodic review of vendors and a plan for requalification if indicated.
- Manufacturing process control: CGT manufacturing processes involve very complex manipulations and activities, which are often performed manually. These require great skill and are crucial for the end product to meet specifications. Processes must be validated and have controls to minimize risks such as cross-contamination or deviations. Auditors must also verify effective training and skill development of personnel performing these operations.
- Lot Genealogy: Chain of identity (COI) and chain of custody (COC) are two critical data sets that maintain the record of all the materials, processes, testing, and outputs of a batch to ensure that patients are treated using the specific product meant for them. Auditors will capture data on who handled the product, what actions were performed, and when and where such actions took place, and they will confirm that a patient's cells or tissue are connected to the resulting drug product with unique identifiers.
- Risk Assessment and Mitigation: Auditors will review risk assessment documentation to ensure that all potential risks in the unique CGT processes have been identified and appropriate mitigations have been put in place. Identifying potential risks in the processes and ensuring proper assessment and analysis of their potential impact is critical to ensuring that all necessary mitigation measures are in place.
- Continuous Improvement: Auditors will confirm that continuous improvement activities are being conducted through monitoring of key performance indicators (KPIs), including process performance, investigations, root cause analysis, CAPA effectiveness, training metrics, and the performance of the supply chain.
Consensus Standards Recognition Program
Another factor to consider when preparing for CGT audits is the recent efforts by the industry to facilitate a risk-based approach in order to streamline and reduce duplicative audits. This is especially important for healthcare institutions and manufacturers involved in the provision of cellular starting material (CSM) collection from patients/subjects for manufacturing purposes.
The American Society for Transplantation and Cellular Therapy convened a working group, the 80/20 Task Force,6 to consider challenges and best practices to address the overlapping requirements facing CGT manufacturers. The Task Force includes representation from pharmaceutical and biotech companies, healthcare institutions, accrediting organizations, and other stakeholders. The report recommended that sites use a standardized approach to audits and gap analysis assessments designed to provide a risk-based evaluation, which will streamline the site qualification processes performed by each manufacturer.
This provides for an abbreviated audit model for sites that have already attained accreditation through agencies such as the Association for the Advancement of Blood & Biotherapies (AABB) and the Foundation for the Accreditation of Cellular Therapy (FACT). Several parts of the safety and quality programs overlap across multiple products, including such things as SOPs for staff organization and oversight, processes for patient identification and tracking, processes for conducting quality investigations and corrective actions, and training requirements for personnel.
Recognizing areas that have already been evaluated and accredited will reduce the audit burden by allowing companies and regulatory agencies to focus on product-specific requirements rather than reevaluating systems that have already been audited in great detail by multiple auditors.
Are YOU Ready For An Audit?
All CGT companies will be subject to audits as they move toward approval and commercialization. The best way to face an audit is to know what to expect and be prepared and ready to provide appropriate answers to inspectors/auditors. For CGT companies, there are additional challenges due to the nature of CGT processes and the specific requirements involved.
References
- Code of Federal Regulations. (2025, January 10). Title 21 of the Code of Federal Regulations (CFR), Part 1271. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271?toc=1
- U.S. Food & Drug Administration. (2023, March 20). Cellular & Gene Therapy Products. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products
- Dougherty, J. (2023, November 1). Considerations for Supporting a GxP Commercial Launch. https://clarkstonconsulting.com/insights/gxp-commercial-launch/
- Shockey, S. (2022, October 26). What Your Company Needs to Know About Preparing for an FDA Inspection. https://clarkstonconsulting.com/insights/preparing-for-an-fda-inspection/
- Patel, S. (2022, October 18). Managing Custom Raw Materials for mRNA Production. https://clarkstonconsulting.com/insights/mrna-production/
- Nikiforow, S., Frigault, M.J., & Frey, N.V. et al. (2023, April). Transportation and Cellular Therapy. Paving the Road for Chimeric Antigen Receptor T Cells: American Society for Transplantation and Cellular Therapy 80/20 Task Force Consensus on Challenges and Solutions to Improving Efficiency of Clinical Center Certification and Maintenance of Operations for Commercially Approved Immune Effector Cell Therapies. https://www.sciencedirect.com/science/article/pii/S2666636723000453
About The Author:
Susan Shockey is a director with Clarkston Consulting and has wide-ranging experience in quality and regulatory compliance. She has 18 years in the life sciences area, focusing on quality systems, quality process improvement, and inspection preparation and remediation. Prior to that, she spent 15 years in quality assurance engineering supporting manufacturing, testing, and validation of NASA space flight and military hardware.