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The demand for advanced therapy medicinal products (ATMPs) is growing fast due to their ability to deliver personalized treatment addressing the root cause rather than treating symptoms. Thanks to the transformative advantage it provides, not offered by conventional treatments, the overall market size for ATMPs is expected to touch USD 21.2 billion by 2028, delivering a 13.2% CAGR for the next seven years.

This has led to several academic institutions and start-ups initiating research and development for cell and gene therapies (CGT). However, CGT manufacturing is a complex process requiring adherence to Good Manufacturing Practice (GMP) and periodic regulatory audits to ensure compliance.

Cell and Gene Therapies

Introduction: Managing the Complexities of CGT Manufacturing with Auditing

Right from cell collection to the delivery of the therapy, each step involves several processes that bring their own risks and require controls.

  1. During the collection process via apheresis, bone marrow aspiration, tumor excision, etc., preparing and monitoring the patient and equipment to yield the appropriate quality raw material is essential.
  2. The raw material and drug products can get affected by factors such as timing, temperature, packaging, and so on and therefore need to be handled, packed, and transported with care.
  3. Certain complex manipulations and activities are performed during the manufacturing process and are crucial for the end product to meet specifications. This is performed manually and requires great skill and consistency.
  4. Understanding the cGMP requirements, equipping the team with the necessary skills, and rigorous training becomes critical.
  5. Lot Genealogy, including 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.
  6. Ensuring that the qualification and performance of vendors meet the required standards, especially since many of them do not operate in a GMP environment.
  7. Standardized processes and controls ensure that the products are fit for the intended use, safe, and comply with regulatory requirements.
  8. Identify risks, put in place mitigation measures, and reduce the risk using an integrated process for both Quality and Risk Management.
  9. Effect continuous Improvement through monitoring of processes and performance, track and trend investigations, root cause, and CAPA, analyze supply chain performance, and manage risks.

For a manufacturer to ensure that each of these processes adheres to the cGMP requirements, auditing becomes crucial. A robust audit process is critical to delivering customer satisfaction, mitigating risks, reducing failure, and increasing operational efficiency.

Benefits of Auditing

Audits can be of two types – internal and external. Treating internal audits with as much seriousness will prepare the CGT companies for external audits. The feedback generated during the audit can help with driving continuous improvements in service standards, thereby enhancing product quality and customer satisfaction.

Some of the benefits of audits include:

  • The observations, feedback, and suggestions offered by the auditor will help identify critical and non-critical areas of improvement.
  • These observations and feedback can be used to create a plan that identifies specific tasks to effect the improvement.
  • Assign responsibilities and establish target dates to ensure follow-up action.
  • Identify skill gaps and train the team to meet the needs as well as answer queries during the audit.
  • Driving overall improvement of processes and workflows, preparing the team for external audit as well as addressing issues of nonconformance early in the lifecycle

By improving the outcome of audits, comply with regulatory standards such as:

  • ICH Q7
  • ISO 9001
  • ISO 13485
  • FDA 21 CFR Part 11
  • US GMPs (USFDA 21 CFR Part 210/211)
  • Health Canada GMPs (Part C, Division 2)

Auditing Checklist

Create an auditing checklist to facilitate a systematic audit of the manufacturing facility covering the following:

Prepare: This is an essential first step to improve the outcome of the audit.

  • Identify the agenda
  • Share the name(s) of the auditor(s) with the team
  • Share the reference standard based on which the audit is to be conducted
  • Outline the areas of interest of the audit
  • Plan the audit such that there is minimal disruption of the facility’s functioning
  • Ensure auditor access to areas of focus
  • Protect the privacy of customers and ensure confidentiality of products and processes

Facilities: The auditors tour the facility to review:

  • Available resources, equipment and related documentation
  • Facility design
  • Inspect all the relevant machinery for their ID numbers and maintenance tags
  • Look for cross-contamination
  • Assess cleanliness
  • Client safety
  • Evacuation protocols
  • Material flow
  • Environmental monitoring and cleaning procedures
  • HVAC system performance
  • Review of SOPs for critical cleanroom operations

The auditors should be accompanied by an employee who is aware of the complete process and can answer accurately any queries they may have.

Personnel: A review of the team members including:

  • Qualifications
  • The training they have received relevant to their roles and responsibilities
  • Review process knowledge

Supply Chain: Review of

  • Standard Operating Procedures (SOPs) for material control
  • Packaging and labeling
  • Storage
  • Shipping
  • Vendor approval
  • Inventory management
  • Process for checking the quality of incoming raw materials and outgoing final products

Quality Assurance (QA):

  • Asses QA processes used from batch record review to product release using a Quality Management System (QMS)
  • Estimate the speed of the checks to assess the competitive advantage
  • Review SOPs for all QA procedures such as deviation management and change control

Quality Control (QC):

  • Evaluate in-process and release testing processes
  • Assess the QC capabilities of CMO to perform onsite tests on-site or whether approval for third parties for outsourcing is required
  • SOPs for environmental monitoring and analytical testing

Outsourcing Control:

  • The services the facility outsources, such as quality control testing or logistics
  • The compliance of external providers to the relevant standards

Documentation:

  • Storage instruments are fit for purpose, are properly qualified, and are compliant
  • Demonstrate a robust maintenance and re-qualification process
  • Maintenance and re-qualification activities conducted during the course of the year

The Role of an EQMS with next-generation Audit, CAPA and Document Management Solutions

For businesses that understand the value of auditing, want to automate and manage the audit lifecycle better, the Audit Management Software from ComplianceQuest is ideal. From scheduling audits to managing the entire audit lifecycle, it allows visibility and traceability through its features such as:

  • Document management
  • Incident reporting
  • Root cause analysis
  • CAPA inputs

Planning and Scheduling Audits: Automate your audit workflow by planning your internal and external audits at a predetermined frequency based on business risk and relevant regulatory requirements. Plan and schedule, document findings and initiate CAPA as required. Calendar views can be set up in the system to alert all stakeholders of scheduled audits and enable them to prepare accordingly. Choose between complex, stringent, or streamlined audits.

Effective Continuous Improvement: The audit management software provides data at their fingertips, enabling businesses to identify gaps and forecast quality performance. Ready access to documents and reports of past audits helps to understand past failure trends and initiate CAPA for continuous improvement, leading to improved performance, customer delight, and thereby, revenue growth.

Stay Compliant: Be compliant with applicable regulatory standards covering different aspects of the product value chain.

Remain Audit and Inspection Ready: A proactive risk management strategy enables businesses to be 100% compliant by identifying gaps, planning, and managing changes, learning from past audits, creating schedules and assigning roles and responsibilities, organizing data and documents, and conducting periodic internal audits. The CQ Audit Management Software provides visibility and transparency at every step of the auditing process.

The pandemic compelled the regulatory bodies to allow remote audits. To find out more about how ComplianceQuest facilitates remote audits, check out:

https://www.compliancequest.com/blog/quality-safety-leaders-audit/
https://www.compliancequest.com/blog/blueprint-for-effective-efficient-remote-audit-process/

Request a demo: https://www.compliancequest.com/online-demo/

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