The Stanford Laboratory for Cell and Gene Medicine is multiproduct biologics manufacturing facility producing cell and gene therapy products for Phase I and Phase II clinical investigations. All products manufactured in the LCGM will be described as required under an Investigational New Drug application (21CFR312.23) with the FDA. Good Manufacturing Practice (GMP) phase appropriate processes and systems were established to ensure products are consistently produced and controlled with quality standards appropriate for intended use.
A Quality Unit ensures all clinical materials manufacturing and testing processes and procedures are created, reviewed, approved and executed in a controlled and documented fashion. Senior Management is ultimately accountable for the effectiveness of the Quality Systems.
Products manufactured in the LCGM adhere to the following GMP/Quality Attributes:
- Products for phase I investigations are developed as outlined in the FDA Guidance for Industry: INDs — Approaches to Complying with CGMP During Phase 1 and products for use in Phase II studies will be manufactured according to the requirements of Good Manufacturing Practice (21CFR 210, 211, 1271)
- All activities are performed per Quality Assurance approved documents. Good documentation practice ensures compliance with GMP requirements.
- Only qualified personnel perform the manufacturing, testing and release of products.
- Starting materials are selected, verified to be obtained from appropriate supplier; certificate of analysis (testing) evaluated; materials inspected and dispositioned (release, reject and quarantine) prior to use.
- Equipment is installed and maintained as per manufacturer’s requirements. Critical process equipment is maintained and calibrated to ensure functionality remains appropriate for intended purpose. All refrigeration and cell culture equipment used in manufacturing and testing is monitored by REES, qualified electronic monitoring system.
- Effective environmental monitoring (eg. personnel, in process, non-viable, surface) and control systems are implemented to maintain a state of control to achieve product quality.
- Segregation of materials, documents, products, samples and equipment is maintained to prevent cross contamination.
- Samples and products are handled, stored and distributed in a manner that ensures quality is maintained throughout the sample or product life cycle.
- Specification for analytical methods are approved by QC based on empirical evidence.
- When performing product lot disposition, a review of manufacturing and analytical execution, adherence to procedure and in process controls are evaluated prior to product release.
- Root cause analysis is employed as required during investigations of deviations and quality/product issues with intent to implement corrective actions designed to prevent reoccurrence. The appropriate determination of cause enables the identification of Corrective Action/Preventive Action (CAPA) with their implementation being monitored for effectiveness.
- Products are released after QA has evaluated and approved the product to have been produced within established process and release requirements.
- GMP outsourced activities are managed through quality agreements between LCGM and contract testing site. The Quality Agreement describes the requirements the contract testing site must comply with to maintain quality of product.
- Proposed changes are evaluated through Change Control where the change is assessed for any regulatory/GMP/product impact and approved prior to implementation.
- An independent audit is periodically conducted to ascertain the effectiveness of the Quality Systems Program.
- Periodic management review of the Quality Systems is required to understand effectiveness and potential improvements of processes and systems.
- Materials are manufactured for pre-clinical safety studies as outlined in the FDA Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products (November 2013)
To provide phase appropriate Quality oversight of LCGM’s GMP manufactured product(s), while fostering continued learning of applicable regulatory guidance and requirements to all stakeholders, and collaborating with all cross-functional departments to ensure sustainable product quality, efficacy, and safety for our patients.