EMA Auditing: Gene Therapy Manufacturing's Secret Weapon

The European Medicines Agency (EMA), a cornerstone of pharmaceutical regulation, provides guidance that significantly impacts gene therapy manufacturing. Robust processes, verified through EMA auditing manufacturing gene therapy, are critical for patient safety. Adeno-associated viruses (AAVs), frequently used as vectors, necessitate meticulous quality control procedures documented and reviewed during audits. Therefore, adherence to Good Manufacturing Practice (GMP) guidelines during EMA auditing manufacturing gene therapy forms the foundation for ensuring the efficacy and safety profile of these novel therapies.

Gene therapy stands at the forefront of medical innovation, promising transformative treatments, and even cures, for a wide range of diseases previously considered intractable. This rapidly evolving field holds immense potential, but its successful translation from the laboratory to the clinic hinges on the establishment of robust and reliable manufacturing processes.

The complexities inherent in gene therapy product development and manufacturing necessitate stringent regulatory oversight. Herein lies the critical role of the European Medicines Agency (EMA) and its auditing function.

The Gene Therapy Revolution: A Landscape of Promise and Complexity

The field of gene therapy has experienced exponential growth in recent years, fueled by advances in vector technology, a deeper understanding of disease mechanisms, and promising clinical trial results.

Gene therapy products, ranging from viral vectors delivering therapeutic genes to cell-based therapies modified with gene editing tools, offer the potential to address the root causes of diseases, rather than merely treating symptoms.

However, the inherent complexity of these products presents unique challenges. Unlike traditional pharmaceuticals, gene therapies often involve living materials, complex manufacturing processes, and long-term effects that are not yet fully understood.

Manufacturing Matters: Ensuring Patient Safety and Product Efficacy

The manufacturing process is arguably the most critical aspect of gene therapy product development. Inadequate control over manufacturing can lead to variability in product quality, reduced efficacy, and, most importantly, potential safety risks for patients.

Robust manufacturing processes are essential to guarantee the identity, purity, potency, and stability of gene therapy products. This includes careful selection of raw materials, meticulous control over each step of the manufacturing process, and rigorous testing to ensure product quality.

EMA Oversight and Auditing: A Pillar of Quality and Compliance

The EMA plays a vital role in regulating gene therapy products in Europe, setting rigorous standards for quality, safety, and efficacy. EMA oversight extends throughout the product lifecycle, from initial clinical trials to post-marketing surveillance.

Auditing is a cornerstone of the EMA's oversight activities. EMA audits assess manufacturers' compliance with Good Manufacturing Practice (GMP) guidelines, ensuring that products are consistently produced and controlled according to quality standards.

These audits are designed to identify potential weaknesses in manufacturing processes, quality control systems, and data management practices. Successful audits demonstrate a manufacturer's commitment to quality and compliance, building confidence among regulators, healthcare professionals, and patients.

Understanding ATMPs: A Regulatory Landscape

Gene therapy products are classified as Advanced Therapy Medicinal Products (ATMPs) within the European regulatory framework. ATMPs are subject to specific regulations and guidelines that reflect their unique characteristics and complexities.

The ATMP framework addresses key aspects such as manufacturing requirements, clinical trial design, and post-marketing surveillance. Understanding the regulatory specificities of ATMPs is essential for manufacturers seeking to develop and commercialize gene therapy products in Europe.

The EMA's Committee for Advanced Therapies (CAT) plays a crucial role in the assessment of ATMPs, providing scientific recommendations on quality, safety, and efficacy to the EMA's Committee for Medicinal Products for Human Use (CHMP).

Gene therapy stands at the forefront of medical innovation, promising transformative treatments, and even cures, for a wide range of diseases previously considered intractable. This rapidly evolving field holds immense potential, but its successful translation from the laboratory to the clinic hinges on the establishment of robust and reliable manufacturing processes.

The complexities inherent in gene therapy product development and manufacturing necessitate stringent regulatory oversight. Herein lies the critical role of the European Medicines Agency (EMA) and its auditing function.

Understanding EMA's GMP Guidelines for Gene Therapy Manufacturing

Having established the importance of the EMA's role, we now turn our attention to the specifics of the Good Manufacturing Practice (GMP) guidelines that govern gene therapy manufacturing within the European Union. These guidelines are not merely suggestions; they are legally binding requirements designed to ensure the safety, efficacy, and consistent quality of gene therapy products.

Decoding GMP Requirements for Gene Therapy Products

The GMP requirements for gene therapy products represent a complex and evolving landscape. Unlike traditional pharmaceuticals, gene therapies often involve biological materials, intricate manufacturing processes, and unique challenges related to scalability and characterization.

It is essential to recognize that gene therapy products fall under the category of Advanced Therapy Medicinal Products (ATMPs). As such, they are subject to specific regulatory requirements outlined in Regulation (EC) No 1394/2007, which supplements the general GMP guidelines laid down in Directive 2003/94/EC and EudraLex Volume 4.

The EMA emphasizes a risk-based approach to GMP compliance, recognizing that the specific requirements may vary depending on the nature of the product, the manufacturing process, and the intended clinical use. This means that manufacturers must conduct thorough risk assessments to identify potential hazards and implement appropriate control measures to mitigate those risks.

Key GMP considerations for gene therapy products include:

• Source Materials: Stringent controls on the sourcing, testing, and characterization of raw materials, including cells, viral vectors, and plasmids.
• Manufacturing Process: Well-defined and validated manufacturing processes with robust in-process controls to ensure consistency and reproducibility.
• Quality Control Testing: Comprehensive quality control testing to verify the identity, purity, potency, and safety of the final product.
• Stability Testing: Thorough stability testing to determine the shelf life of the product and ensure that it remains safe and effective throughout its intended use.

EMA's Expectations for Manufacturing Processes

The EMA places significant emphasis on control and reproducibility in gene therapy manufacturing. Manufacturing processes must be robust, well-defined, and consistently executed to ensure that each batch of product meets the required quality standards.

This requires a deep understanding of the critical process parameters (CPPs) and critical quality attributes (CQAs) that can impact product quality. CPPs are process variables that can affect CQAs, which are the physical, chemical, biological, or microbiological properties that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

Manufacturers must establish and maintain a robust process validation program to demonstrate that their manufacturing processes are capable of consistently producing product that meets pre-defined quality attributes. This program should include:

• Process Design: A thorough understanding of the process and its critical parameters.
• Process Qualification: Demonstration that the process is capable of consistently producing product that meets the required quality standards.
• Continued Process Verification: Ongoing monitoring of the process to ensure that it remains in a state of control.

The Vital Role of Quality Control and Quality Assurance Systems

Quality Control (QC) and Quality Assurance (QA) are integral to GMP compliance for gene therapy products. QC encompasses the testing and analysis of raw materials, in-process samples, and finished products to ensure that they meet pre-defined quality standards.

QA, on the other hand, is a broader concept that encompasses all activities designed to ensure that products are consistently manufactured to meet their intended use. This includes establishing and maintaining a quality management system (QMS) that covers all aspects of the manufacturing process, from raw material sourcing to product release.

Key elements of a robust QMS include:

• Document Control: Maintaining accurate and up-to-date documentation of all manufacturing processes, procedures, and test results.
• Change Control: Implementing a formal change control system to manage any changes to the manufacturing process or QMS.
• Deviation Management: Investigating and documenting any deviations from established procedures or quality standards.
• Corrective and Preventive Actions (CAPA): Implementing CAPAs to address the root causes of deviations and prevent their recurrence.

Regulatory Compliance: Adhering to EMA Standards

Compliance with EMA standards is not merely a matter of paperwork; it is a fundamental requirement for ensuring the safety and efficacy of gene therapy products. Manufacturers must have a deep understanding of the applicable regulations and guidelines and must implement systems and procedures to ensure ongoing compliance.

This includes:

• Staying Informed: Keeping abreast of the latest regulatory updates and guidance documents issued by the EMA and other relevant authorities.
• Training: Providing comprehensive training to all personnel involved in the manufacturing process.
• Internal Audits: Conducting regular internal audits to assess compliance with GMP requirements.
• External Audits: Preparing for and responding to external audits conducted by the EMA or other regulatory agencies.

Ultimately, a commitment to regulatory compliance is essential for building trust with patients, healthcare professionals, and regulatory authorities, and for ensuring the long-term success of the gene therapy field.

Having explored the intricate regulatory landscape and the foundational GMP guidelines, it's time to turn our attention to the practical application of these standards. This is where the power of auditing comes into play, acting as a crucial mechanism for verifying compliance and identifying areas for improvement. Audits aren't merely exercises in ticking boxes; they are dynamic assessments that provide a snapshot of a manufacturing facility's adherence to established protocols and its commitment to product quality and patient safety.

The Power of Auditing: Key Areas and Focus Points

Auditing is more than just a regulatory requirement; it's a critical tool for ensuring the safety, efficacy, and consistency of gene therapy products. It provides an objective assessment of a manufacturer's compliance with EMA regulations and GMP standards, highlighting areas of strength and identifying potential vulnerabilities.

Risk Assessment and Mitigation

Auditing plays a vital role in evaluating a manufacturer's risk assessment and mitigation strategies. A robust risk assessment should identify potential hazards throughout the manufacturing process, from raw material sourcing to final product release.

Auditors will examine the methodology used for identifying and evaluating risks, as well as the effectiveness of the implemented mitigation measures. This includes assessing the adequacy of control measures, such as equipment maintenance, personnel training, and process monitoring.

Verification of Sterility Testing Procedures

Sterility is paramount in gene therapy manufacturing, and audits must thoroughly verify the effectiveness of sterility testing procedures. Auditors will scrutinize the methods used for sterility testing, ensuring they are validated and compliant with pharmacopeial standards.

This includes verifying the use of appropriate controls, the qualification of personnel, and the maintenance of accurate records. Any deviations or anomalies in sterility testing must be thoroughly investigated and addressed.

Batch Release Documentation

A meticulous review of batch release documentation is a critical component of any gene therapy audit. Auditors will examine all documentation related to the manufacturing and testing of a specific batch, ensuring it meets all regulatory requirements and GMP standards.

This includes reviewing raw material certificates of analysis, manufacturing records, quality control testing results, and deviation reports. The batch release documentation should provide a complete and accurate record of the entire manufacturing process, demonstrating that the product meets all predefined specifications.

Raw Material Sourcing and Management

The quality and traceability of raw materials are essential for ensuring the safety and efficacy of gene therapy products. Auditors will assess the manufacturer's processes for sourcing, testing, and managing raw materials.

This includes verifying the qualification of suppliers, the implementation of appropriate quality control measures, and the maintenance of accurate records. Traceability is crucial, allowing auditors to trace the origin of each raw material used in the manufacturing process.

Cell Bank Maintenance and Characterization

Cell banks are often a critical starting material for gene therapy products, and their proper maintenance and characterization are essential. Auditors will examine the procedures for establishing, maintaining, and characterizing cell banks, ensuring they meet all regulatory requirements.

This includes verifying the identity, purity, and genetic stability of the cells. Comprehensive characterization data should be available to demonstrate the suitability of the cell bank for use in manufacturing.

Viral Vector and Plasmid Production and Quality Control

Viral vectors and plasmids are commonly used as delivery vehicles in gene therapy, and their production and quality control require careful attention. Auditors will assess the manufacturer's processes for producing and testing viral vectors and plasmids, ensuring they meet all predefined specifications.

This includes verifying the titer, purity, and infectivity of the vectors. Robust quality control measures are essential to ensure the consistency and reliability of the viral vector or plasmid product.

Data Integrity and Electronic Record Management

Data integrity is a growing concern in the pharmaceutical industry, and gene therapy manufacturing is no exception. Auditors will assess the manufacturer's systems for ensuring data integrity, including electronic record management systems.

This includes verifying the security, accuracy, and reliability of electronic data. Audit trails should be in place to track all changes made to electronic records. The principles of ALCOA (Attributable, Legible, Contemporaneous, Original, and Accurate) should be fully implemented in all data management practices.

CMOs and EMA Oversight: A Collaborative Approach to Gene Therapy Manufacturing

The gene therapy sector is experiencing unprecedented growth, driving innovation and offering hope for patients with previously untreatable diseases. This rapid expansion has led to an increasing reliance on Contract Manufacturing Organizations (CMOs) to handle the complexities of gene therapy product manufacturing.

However, this reliance introduces unique challenges that require careful consideration and a collaborative approach between sponsors, CMOs, and regulatory agencies like the EMA.

The Rising Prominence of CMOs in Gene Therapy

Gene therapy manufacturing is a highly specialized field, demanding expertise in areas such as viral vector production, cell culture, and aseptic processing. The infrastructure and technical knowledge required are significant, making it challenging for many companies, especially smaller biotechs, to establish in-house manufacturing capabilities.

CMOs offer a viable solution, providing access to established facilities, experienced personnel, and validated processes. This allows companies to focus on research, development, and clinical trials, accelerating the path to market.

The partnership between sponsors and CMOs also brings potential risks if not managed correctly. This is why the EMA provides oversight and expectations for sponsors when working with CMOs.

EMA's Expectations for Sponsor Oversight of CMOs

The EMA places a strong emphasis on the sponsor's responsibility for ensuring that CMOs adhere to GMP standards. This oversight is not merely a formality; it is a critical element in safeguarding product quality and patient safety.

Auditing is a cornerstone of effective oversight. Sponsors are expected to conduct thorough and regular audits of their CMOs to assess compliance with GMP regulations and to identify any potential deficiencies.

These audits should be comprehensive, covering all aspects of the manufacturing process, from raw material sourcing to final product release.

Audits should be performed by qualified individuals with expertise in gene therapy manufacturing and GMP requirements.

The frequency of audits should be risk-based, taking into account the complexity of the manufacturing process, the CMO's track record, and any identified areas of concern.

Beyond auditing, sponsors are responsible for providing clear specifications and instructions to their CMOs, ensuring that they understand the requirements for manufacturing their gene therapy product. This includes defining critical process parameters, quality control testing methods, and release criteria.

Sponsors must also establish robust communication channels with their CMOs to facilitate the timely exchange of information and the resolution of any issues that may arise.

The Role of the Qualified Person (QP) at CMOs

The Qualified Person (QP) plays a pivotal role in ensuring GMP compliance at CMOs. The QP is an individual who is responsible for certifying that each batch of a medicinal product has been manufactured and controlled in accordance with GMP requirements.

The QP must possess the necessary qualifications, training, and experience to fulfill this responsibility.

At CMOs, the QP acts as an independent check on the manufacturing process, ensuring that all procedures are followed correctly and that the product meets the required quality standards.

The QP is responsible for reviewing batch records, analytical data, and other relevant documentation to verify compliance with GMP.

The QP's certification is a prerequisite for the release of any gene therapy product manufactured at a CMO.

The EMA expects sponsors to ensure that the QP at their CMO is fully qualified and has the necessary authority to make independent decisions regarding product quality. This includes providing the QP with access to all relevant information and ensuring that the QP is not subject to undue influence from the CMO's management.

Collaborative Success in Gene Therapy Manufacturing

Effective collaboration between sponsors, CMOs, and regulatory agencies is essential for ensuring the safety, efficacy, and quality of gene therapy products.

Sponsors must take ownership of their responsibility for overseeing their CMOs, conducting thorough audits, and establishing clear communication channels.

CMOs must commit to adhering to GMP standards, providing transparent access to their facilities and processes, and working collaboratively with sponsors to address any issues that may arise.

Regulatory agencies like the EMA play a vital role in setting standards, conducting inspections, and providing guidance to the industry.

By working together, these stakeholders can ensure that gene therapy products are manufactured to the highest quality standards, delivering hope and improving the lives of patients around the world.

Learning from Experience: Case Studies in EMA Auditing

The true value of EMA auditing isn't just theoretical; it's demonstrated in tangible outcomes. By examining real-world scenarios, we can clearly see how rigorous auditing safeguards gene therapy manufacturing, and conversely, how failures in oversight can lead to significant repercussions. Let's delve into some illustrative case studies.

The Positive Impact: Preventing Manufacturing Issues

Imagine a hypothetical, yet representative, scenario: A small biotech company specializing in adeno-associated virus (AAV) vector production is preparing for its first EMA inspection. The company proactively engages in rigorous internal audits, meticulously reviewing their standard operating procedures (SOPs), batch records, and quality control data.

During the EMA inspection, auditors identify minor deviations in temperature monitoring within a critical storage freezer. While these deviations haven't yet impacted product quality, the audit team flags them as a potential risk.

The company immediately implements corrective actions, including upgrading the temperature monitoring system and retraining personnel. This swift response, driven by the initial identification during the internal audit and reinforced by the EMA's findings, prevents a larger temperature excursion that could have compromised an entire batch of viral vectors. This proactive approach, fostered by diligent auditing, saves the company time, resources, and reputational damage. It also ensures that the clinical trial continues without interruption, ultimately benefiting patients.

This case exemplifies how effective EMA auditing, coupled with a strong internal audit program, can proactively identify and mitigate potential manufacturing issues before they escalate into serious problems.

The Consequences of Inadequate Oversight

Contrast this with a scenario where a company takes a more relaxed approach to auditing. Perhaps due to resource constraints or a lack of understanding of GMP requirements, their internal audit program is superficial and infrequent.

During an EMA inspection, auditors uncover significant deficiencies in the company's aseptic processing techniques. Environmental monitoring data reveals recurring contamination events, but these have not been adequately investigated or addressed.

Further investigation reveals that the company's personnel lack proper training in aseptic techniques, and that critical equipment is not being properly maintained. This systemic failure in quality control leads to the rejection of multiple batches of gene therapy product, halting clinical trials and raising serious concerns about patient safety.

In this instance, the consequences are severe. The company faces regulatory sanctions, including potential fines and restrictions on its manufacturing activities. Its reputation is tarnished, making it difficult to attract investors or secure future partnerships. More importantly, patients are denied access to potentially life-saving therapies.

This case underscores the critical importance of robust auditing and a strong commitment to GMP compliance. Inadequate oversight not only jeopardizes product quality but can also have devastating consequences for companies and patients alike.

The Role of Data Integrity

Another recurring theme in EMA audits, and a frequent source of findings, is data integrity. Consider a case where an investigation reveals incomplete or altered records related to critical manufacturing parameters.

Perhaps electronic audit trails are disabled, or paper records are improperly corrected without proper documentation. The EMA views data integrity breaches as a serious threat to product quality and patient safety because if the data is unreliable, there is no way to trust that the manufacturing process is under control.

Companies found to have data integrity issues face severe consequences, including warning letters, import alerts, and even criminal prosecution. These cases serve as a stark reminder of the need for robust data governance practices and a culture of honesty and transparency within gene therapy manufacturing organizations.

Learning from Others

These case studies, while simplified, highlight the real-world impact of EMA auditing. By learning from the experiences of others – both positive and negative – gene therapy manufacturers can strengthen their own quality systems and ensure compliance with regulatory requirements.

Proactive auditing, a strong commitment to GMP, and a culture of data integrity are essential for success in the gene therapy field. Only through rigorous oversight can we ensure that these innovative therapies are manufactured safely and effectively, ultimately benefiting the patients who rely on them.

Contrast this with the potential consequences of neglecting robust auditing practices. Instances of inadequate oversight serve as stark reminders of what's at stake. By learning from both successes and failures, manufacturers can glean valuable insights for strengthening their own quality systems. This knowledge then informs a proactive approach to EMA audits, setting the stage for a smoother, more successful inspection.

Preparing for Success: Best Practices for EMA Audits

The key to navigating EMA audits successfully lies in meticulous preparation and a commitment to continuous improvement. It's not merely about passing an inspection; it's about demonstrating a robust quality system that ensures patient safety and product efficacy. A well-prepared organization can approach an audit with confidence, showcasing its commitment to GMP compliance.

Proactive Documentation Review

Documentation is the backbone of any successful EMA audit. A thorough review of all relevant documentation is paramount. This includes, but isn't limited to:

• Standard Operating Procedures (SOPs): Ensuring SOPs are up-to-date, accurate, and consistently followed.

• Batch Records: Verifying complete and accurate records of all manufacturing activities.

• Quality Control Data: Confirming the integrity and reliability of all testing data.

• Validation Reports: Demonstrating that manufacturing processes are validated and consistently produce the desired results.

This review should be conducted well in advance of the audit, allowing ample time to identify and address any gaps or inconsistencies. A proactive approach to documentation minimizes the risk of findings during the actual inspection.

Empowering Staff Through Comprehensive Training

A well-trained staff is crucial for a successful audit outcome. All personnel involved in gene therapy manufacturing should receive comprehensive training on:

• GMP Regulations: Understanding the specific GMP requirements applicable to gene therapy products.

• SOPs: Demonstrating proficiency in following established procedures.

• Data Integrity: Recognizing the importance of accurate and reliable data recording.

• Audit Preparedness: Understanding the audit process and their roles during the inspection.

Training should be regularly updated to reflect changes in regulations or internal procedures. Employees should be able to articulate their understanding of GMP principles and how they apply to their specific roles. Investing in comprehensive staff training fosters a culture of quality and compliance.

Mastering the CAPA Process: Responding to Audit Findings

No matter how well-prepared an organization is, audit findings are inevitable. The key is to have a robust Corrective and Preventive Action (CAPA) system in place to address these findings effectively.

• Prompt Investigation: Conducting a thorough investigation to determine the root cause of the finding.

• Effective Corrective Actions: Implementing immediate actions to correct the identified issue.

• Preventive Actions: Developing and implementing strategies to prevent the recurrence of similar issues.

• Documentation and Verification: Documenting all CAPA activities and verifying their effectiveness.

The CAPA system should be designed to drive continuous improvement, ensuring that the organization learns from its mistakes and strengthens its quality system. Timely and effective implementation of CAPAs demonstrates a commitment to addressing issues proactively and preventing future occurrences.

By diligently focusing on these key areas – proactive documentation review, comprehensive staff training, and a robust CAPA system – gene therapy manufacturers can significantly enhance their preparedness for EMA audits and solidify their commitment to quality, safety, and regulatory compliance.

Contrast this with the potential consequences of neglecting robust auditing practices. Instances of inadequate oversight serve as stark reminders of what's at stake. By learning from both successes and failures, manufacturers can glean valuable insights for strengthening their own quality systems. This knowledge then informs a proactive approach to EMA audits, setting the stage for a smoother, more successful inspection.

Looking Ahead: The Future of EMA Auditing in Gene Therapy

The gene therapy landscape is rapidly evolving, and with it, the demands placed on regulatory oversight. The future of EMA auditing in this sector will be shaped by emerging trends that demand a proactive and adaptive approach. These trends include not only an increased focus on data integrity and process validation but also the integration of new technologies and manufacturing paradigms.

Heightened Focus on Data Integrity

Data integrity has become a cornerstone of GMP compliance. The EMA is increasingly scrutinizing data management practices to ensure that all data generated during the manufacturing process is complete, accurate, consistent, and reliable. This heightened focus reflects a growing recognition that the integrity of data is directly linked to product quality and patient safety.

Strengthening Data Governance

Future audits will likely place greater emphasis on data governance frameworks. Manufacturers need to demonstrate robust systems for data capture, storage, retrieval, and security. This includes implementing audit trails, access controls, and data backup procedures. Expectations are rising for manufacturers to adopt a "data lifecycle" approach, managing data from its creation to its eventual archiving or deletion.

Combating Data Manipulation

The EMA is acutely aware of the potential for data manipulation, whether intentional or unintentional. Audits will increasingly involve sophisticated techniques to detect anomalies and inconsistencies in data sets. This might involve advanced statistical analysis or forensic data reviews. Companies should invest in training their staff on data integrity principles and fostering a culture of transparency and accountability.

The Impact of New Technologies and Manufacturing Approaches

The gene therapy field is characterized by constant innovation, with new technologies and manufacturing approaches emerging regularly. These advancements present both opportunities and challenges for EMA auditing.

Auditing Advanced Manufacturing Processes

New manufacturing paradigms, such as continuous manufacturing and closed systems, require novel auditing strategies. Traditional auditing methods may not be sufficient to assess the control and robustness of these advanced processes. Auditors will need to develop expertise in these technologies and adapt their auditing techniques accordingly.

Embracing Digitalization

The increasing digitalization of manufacturing operations presents opportunities for more efficient and effective auditing. Real-time data monitoring and analysis can provide auditors with valuable insights into process performance and control. However, digitalization also introduces new risks, such as cybersecurity threats and data breaches. Audits will need to address these risks and ensure that adequate security measures are in place.

Adapting to Personalized Medicine

The rise of personalized medicine poses unique challenges for EMA auditing. Gene therapies tailored to individual patients require highly flexible and adaptable manufacturing processes. Audits will need to assess the controls in place to ensure the consistency and quality of these personalized products. This requires a shift from traditional batch-based auditing to a more process-oriented approach.

The future of EMA auditing in gene therapy will demand a proactive, adaptive, and data-driven approach. Manufacturers must embrace new technologies, strengthen their data governance frameworks, and invest in training their staff. By doing so, they can ensure that they are well-prepared for future audits and can continue to deliver safe and effective gene therapies to patients.