Endologix is a developer and manufacturer of minimally invasive treatments for vascular diseases and focuses on the development and marketing of its patented technology for the treatment of Abdominal Aortic Aneurysms (AAA). Nellix is an investigational EndoVascular Aneurysm Sealing (EVAS) system designed for the treatment of infrarenal abdominal aortic aneurysm (AAA). EVAS is the next generation AAA therapy intended to treat more anatomies than currently approved endovascular stent graft devices and is the only technology whose operating principle is centered on sealing the aneurysm sac.
Nellix was designed to address unmet clinical needs and potentially reduce the need for secondary interventions following endovascular AAA repair. In initial clinical trial experience involving 47 patients outside of the United States, 100% implant success was observed. Physician feedback has been positive, particularly as it relates to ease of use and versatility to treat both standard and more challenging aneurysm anatomies.
Endologix submitted an Investigational Device Exemption (IDE) for the Nellix investigational device at the end of May 2012 and updated their pending CE mark submission. They required engineering and regulatory submission support to ensure during the delivery that proper temperature is maintained from point of manufacture to point of use.
The focus of the engagement was:
- Assess risk on device and product using currently available characterization studies
- Set acceptable ranges and durations of allowable temperature exposures during transport
- Document risks and design additional characterization studies as needed
- Create validation master plan for distribution operations
- Qualify pallet and small parcel thermal packaging
- Recommend visual controls (indicators and markers) for health care professionals to assess storage and handling methods
- Prepare the appropriate sections in IDE to support controlled-termperature logistics network design and validation
Value to Endologix
- Assist in identification of acceptable temperature ranges for shipments
- Design characterization studies to support filing for wider temperature ranges
- Document the validation approach for both logistics processes and thermal packaging
- Enable successful filing on Nellix
- Provide recommendations on cold chain logistics, packaging, and related monitoring technology
- Increase chance of approval for Nellix by documenting validation of cold chain logistics
- Oversight of hospital handling procedures to mitigate risks of sub-optimal deployment by using visual indicators
- Preparation of team for discussing cold chain logistics validation and thermal packaging qualification with regulators
- Conduct risk assessment of proposed commercial cold chain logistics process. The current thermal qualification data, product characteristics, logistics network, and regulatory guidance was assessed to identify opportunities to mitigate any regulatory exposure. A phased approach was designed to address near term launch plans and intermediate and long-term improvements.
- Design characterization studies to mitigate any high risks. Any high risks identified required a characterization study to determine either the nature of the risk (product quality or patient safety) or eliminate the risk (regulatory compliance). The approach for the characterization studies was documented along with the risk assessment in the validation master plan.
- Document risk assessment, characterization studies, and validation approach in validation master plan. Created a validation master plan that documented the processes and packaging to be validated and the appropriate approach. The main objective was to outline in sufficient detail the approach to developing documented evidence the system (process and packaging) consistently performed as designed in a reproducible way to meet predetermined quality attributes (i.e. acceptance criteria for the protocols) based on product characteristics.
- Select ‘off the shelf’ thermal packaging solutions for validation. ‘Off the shelf’ pallet and small parcel shipping solutions were selected based on the product and validation requirements. The selection process included product capabilities, ease of validation, and total delivered cost.
- Validate thermal packaging solutions to industry standards. The ‘off the shelf’ thermal packaging system selected was validated to the approach outlined in the validation master plan. Operational Qualification reports were provided by supplier and reviewed by both Modality Solutions and Endologix for inclusion into validation package. The Performance Qualification (PQ) protocols and reports were written by Modality Solutions and executed and approved by Endologix personnel.
- Prepare the sections in the IDE on cold chain logistics for internal approval and submission. The appropriate sections of the IDE as identified by regulatory subject-matter experts at Endologix were written by Modality Solutions and approved by Endologix. The sections provided detailed results of the validation process to allow the regulators to understand the risks, documented evidence, and controls required for the logistics process.
- Conduct training to prepare for discussion during IDE approval process. A training session for Endologix personnel allow with preparatory sessions to ‘role play’ the inspection process were conducted. A single page review of requirements for partners in the supply chain (e.g. freight forwarders, 3PL providers, customers, etc.) was created to summarize handling requirements.
- Source and validate visual controls to provide oversight on hospital handling procedures to point of use. Visual controls based on product requirements (e.g. freeze indicator, threshold indicator, time-temperature indicator, etc.) will be sourced and validated. The validation will reply primarily on manufacture data reviewed by Modality Solutions and Endologix and concurrent performance qualification (PQ) collected on first article commercial shipments.
NELLIX INVESTIGATIONAL DEVICE EXEMPTION (IDE) WAS APPROVED IN DECEMBER 2013!
- Risk assessment identified several high risks that were mitigated by characterization studies
- Validation master plan was reviewed successfully by regulators and outlined risks, approach and results to validation activities
- "Off the shelf" thermal packaging was successfully qualified to new standards set by updated quality management system
- Section of IDE covering cold chain logistics was reviewed with no comments
- Visual indicators showing health care professionals that proper shipping and handling was conducted was sourced and validated
- Special handling training materials were shared with supply chain partners and healthcare professionals detailing proper handling and interpreting visual indicators.