Adello Biologics



Background
Adello Biologics (Adello), formerly Therapeutic Proteins International (TPI), is an innovative US-based pure-play biosimilar company focused on developing recombinant proteins and antibody products for major regulated markets and strategic markets globally. Their vision is to make biosimilar medications affordable. Adello utilizes its proprietary, single-use technology platform, MayaBio®, to build a strong pipeline of biosimilar candidates. With headquarters in New Jersey and manufacturing in Chicago, Adello is led by a team of experienced industry leaders. Their patented bioprocessing technology allows Adello to operate nimbly in a rapidly evolving global market.

The Adello management team requested Modality Solutions’ assistance with their BLA filing for Filgrastim and Pegfilgrastim drug products (pre-filled syringes and vials) with the FDA. The drug substance is manufactured by Adello in Chicago, Illinois; drug product fill-finish operations are conducted at Althea in San Diego, California; packaging and labeling is completed by Adello in Chicago, Illinois; and final packaging is conducted by PCI in Philadelphia, Pennsylvania.

    Modality Solutions’ assistance included:
    • Acting as shipping validation experts in support of BLA
    • Providing shipping strategy development
    • Analyzing thermal packaging and shipping method selections
    • Writing validation protocols
    • Supporting execution of protocols
    • Writing validation reports
    The aim of the project was to execute and summarize the shipping lane validation studies prior to the BLA submission. Changes to the planned filing date allowed for greater preparation and increased the submission information—avoiding significant questions and potentially proscriptive remedies imposed by the FDA.

    Objectives
    The focus of the engagement was to:
    • Review existing qualification reports and assist in in-progress shipping validation studies
    • Select appropriate thermal packaging and pallet design
    • Author a transportation Validation Master Plan (VMP) for each molecule
    • Design and execute operational qualifications (OQ) for shipping lanes
    • Design and execute performance qualifications (PQ) on remaining shipping lanes
    • Write validation reports for all shipping lanes
    • Design and execute plunger movement studies for pre-filled syringes
    • Summarize validation activities for both molecules in separate VMPs
    Progress toward the objectives was and will continue to be measured by:
    • US supply chain map and process flow diagram
    • Assessment of shipping validation protocols, reports, and pack out instructions
    • In-progress shipping lane PQ studies
    • Approved transportation VMPs
    • OQ protocols and reports for shipping lane validation
    • PQ protocols and reports for shipping lane validation
    • Plunger movement study protocols and reports for pre-filled syringes
    • Summaries on validation activities for both molecules in VMP

    Value to Adello Biologics
    The value of this project was multifold, including:
    • Access to our experience in preparing multiple biologics and biosimilars for FDA review and approval
    • Proven success in preparing for BLA submissions in accelerated time frames
    • Modality Solutions’ proprietary sophisticated transport simulation laboratory (TSL) in an FDA-approved, GMP-compliant facility in Bloomington, Indiana

    Methodology
    Our detailed approach for the BLA filing with the FDA included:
    Mapping US supply chain and creating the process flow diagram. The US supply chain map was used to create the process flow diagram. The process flow diagram shows the detailed steps in the US supply chain that was designed into the OQ simulated transport study.

    Selecting thermal packaging for remaining lanes that had not been started. The shipping lane validations that had not been started required the selection of either pre-qualified active or passive thermal packaging. The selections were based on the supply chain and process map requirements and timing of BLA filing.

    Assessing protocol design and assisting in execution for two (2) shipping lanes already in progress. The two shipping lane validation studies already in progress were assessed for completeness and suitability. Modality Solutions assisted in completing the execution of the protocols as required.

    Assessing thermal packaging operational qualification. The thermal packaging protocols, reports, and pack out instructions for the active or passive thermal packaging systems selected for the shipping validation studies were gathered. The manufacturer specifications and associated data packages were evaluated against acceptance criteria. These qualification studies are still to be included in the VMP as appropriate.

    Developing transportation VMP. The VMP is a document that describes how the OQ and the PQ are authorized, authored, approved for content, and issued for execution for each molecule. The completed documentation is compiled for review and approval. Responsibilities are declared; risks are identified; and the validation approach is documented. Currently the VMP is completed for the Filgrastim and under review for the Pegfilgrastim.

    Authoring and executing OQ protocols and completing OQ reports. A OQ protocol was written for Filgrastim drug product transportation. The OQ protocol was executed in Modality Solutions TSL to simulate drug product transportation. An OQ report was authored including results from the OQ simulation. Similar OQs will be executed for Pegfilgrastim drug substance and drug product.

    Authoring and executing plunger movement study protocols and completing reports. Modality Solutions authored and executed protocols for pre-filled syringe plunger movement studies and authored reports.

    Completing shipping lane PQ reports. Modality Solutions authored reports for the DS shipping lane qualifications already in progress. The data packages were reviewed against (1) the acceptance criteria and (2) the report detailing the qualified temperature range. The reports confirmed adequate temperature control by the thermal packaging in the shipping lanes.

    Results
    Results include:
    • Modality Solutions recommended refrigerated trucks for DP lanes and stayed with same DS passive shipper for both molecules.
    • Previous shipping validation protocols were assessed for completeness and suitability:
      • Two Filgrastim drug substance protocols were previously executed in full and evaluated as suitable. Both protocols have been successfully closed.
      • Filgrastim drug product protocol was partially executed. Modality Solutions recommended aborting this protocol and completing a drug product OQ simulation prior to PQ studies.
    • A process flow diagram based on the US supply chain map provided details to include in OQ simulations.
    • VMP provided overall strategy for shipping validation efforts.
    • Filgrastim drug product OQ simulation was conducted and has provided positive results for functionality and product quality to date.
    Further, multiple deliverables are in-progress for both Filgrastim and Pegfilgrastim shipping validations and BLA submissions including:
    • Preparing VMP. An appropriate summary of validation activities for both molecules will be written by Modality Solutions and approved by Adello. The VMP will provide detailed results of the validation process to allow the regulators to understand the risks, documented evidence, and any controls required for the logistics process.
    • Authoring shipping lane PQ protocols. A PQ protocol will be written for each remaining shipping lane. Distribution operations and transportation partners will execute the protocols and report results. These results will be included in the PQ reports for inclusion in the VMPs.
    • Supporting the execution of the shipping PQ studies. Modality Solutions will provide support to Adello and contract partners to execute the PQ protocols for the shipping lane validation. Execution support will cover: protocol design, documentation requirements, and training on pack out instructions as well as other handling requirements.
    • Completing shipping lane PQ reports. Modality Solution will author reports for shipping lane validations still to be executed. The data packages will be reviewed against (1) the acceptance criteria and (2) for the DS shipping lane, the report detailing the qualified temperature range. The reports will confirm adequate temperature control by the thermal packaging or refrigerated trucks in the shipping lanes.