Governance Plan for the HHS Centers for Innovation in Advanced Development and Manufacturing

Background

In June 2012, HHS established three new Centers for Innovation in Advanced Development and Manufacturing (CIADM) to develop and manufacture medical countermeasures used to protect health in emergencies, with the ability to transition quickly and cost effectively between products. The HHS CIADM will aid in bringing new medical countermeasures, such as vaccines and therapeutics, to the market faster and help to train the biopharmaceutical workforce needed in the future.

Overseen by the Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response (ASPR), the contracts with each HHS CIADM can be renewed for up to a total of 25 years. This represents a long-term commitment on the part of the biopharmaceutical / pharmaceutical industry to public-private partnerships that establish capabilities to address significant national security threats.

Under the contracts, each HHS CIADM will retrofit existing facilities or build new ones to incorporate flexible, innovative manufacturing platforms that can be used to manufacture more than one product. The facilities will use modern cell and recombinant-based vaccine technologies that have the potential to rapidly produce vaccines and therapeutics not only for pandemic influenza but also other natural and man-made Chemical, Biological, Radiological and Nuclear (CBRN) threats.

The three objectives of the HHS CIADM program to provide:

  • core services, on a routine basis, for the advanced development and manufacturing of CBRN biopharmaceutical countermeasures supported by the U.S. Government;
  • in an emergency, necessary U.S.-based surge capacity to respond to an emerging infectious disease, pandemic influenza, and currently known or unknown threats; and
  • biopharmaceutical oriented workforce development through training programs aligned with current regulatory guidelines.

HHS CIADM Governance Plan

In December 2012, BARDA finalized a HHS CIADM Governance Plan that outlines the process to ensure that HHS CIADM support of medical countermeasures are evaluated by the U.S. Government in a consistent manner that is aligned with the mission and requirements of BARDA and the PHEMCE. This plan is the basis for procedures and checklists that will enable medical countermeasure program managers across the U.S. Government to evaluate and request the use of the HHS CIADM capabilities in support of their projects.

The following table outlines (at a high-level) how emergency medical countermeasure program managers from across the U.S. Government will gain access to the HHS CIADM core services.

Semi-annual Request for Projects
  • Request initiated by the HHS CIADM Program within ASPR/BARDA
  • MCM Program Leads across the U.S. Government bring forward potential projects [e.g. BARDA/CBRN, NIH/NIAID, DOD/JPEO-CBD]
Project Review
  • Proposed projects brought forward to the HHS Advanced Development and Manufacturing (ADM) Steering Committe for consideration
  • HHS ADM Steering Committee approves projects to proceed to the HHS CIADM.
Project Assignment & Execution
  • Projects competitively bid among the HHS CIADM Contractors
  • Project awarded to specific HHS CIADM Contractor [overall best value]
  • HHS CIADM Contractor performs the work outlined in the project plan

Note: A 'project' is a Request for Task Order Response [RTOR] to utilize a set of HHS CIADM core services to assist existing U.S. Government contractors working on the advanced development and manufacturing of medical countermeasures.

HHS Advanced Development & Manufacturing Steering Committee

As the table in the previous section indicates, the governance process is overseen by the HHS Advanced Development and Manufacturing (ADM) Steering Committee [or the HHS-ASC]. This is a senior-level decision and coordination body for all HHS CIADM policy and product-level concerns. The Chairperson of the HHS-ASC is the BARDA Director with standing membership from across the PHEMCE.

There are four primary assessment and decisional functions of the HHS-ASC:

  1. Review and advise the HHS-ASC Chairperson on the prioritization of medical countermeasure advanced development and manufacturing projects within the HHS CIADM;
  2. Oversight and trouble-shooting of medical countermeasure advanced development and manufacturing projects being executed by the HHS CIADM;
  3. Monitor the overall functionality ('health') of the HHS CIADM program and infrastructure; and
  4. Charter Working Groups to make timely and informed recommendations to the HHS-ASC on matters of relevance.

Other roles will be identified on an as needed basis, and would include adjudication of concerns throughout the process.

HHS CIADM CORE SERVICES

For reference, the following table outlines the advanced development and manufacturing core services that are available through HHS CIADM contracts administered by BARDA.

HHS CIADM Core ServiceDefinition/ Description of Core Service
Program /Project Management Support The discipline of planning, organizing, motivating, and controlling resources to achieve specific goals.
Regulatory Affairs Support Provide guidance in establishment of regulatory filing strategy and license submissions to FDA.
Quality Systems & Quality Control Support Systems are in place and meet current Good Manufacturing Practices (cGMP) to ensure that products are manufactured to meet the identity, strength, quality, and purity they purport.
Non-Clinical Studies Development Early development studies to determine the manufacture, safety, toxicity and efficacy of the drug product to determine proof of concept.
Clinical Studies Development Human Clinical Trials proceeding from Phase 1 safety and dose studies through Phase 3 efficacy and safety studies with a potential new vaccine drug product.
Upstream Process Development & Optimization The entire process from early cultivation, banking, expansion and collection of intermediate product.
Downstream Process Development & Optimization The process when upstream product is purified to meet certain purity, quality, and yield requirements.
Master & Working Cell Bank Accession & Validation Preparation of a homogeneous population of cells and stored for future production use.
Master & Working Virus Seed Banking and Validation Preparation of a homogeneous population of virus and stored for future production use.
Pilot Bulk Manufacturing of Clinical Investigational Lots Manufacturing development step to provide product, usually at a small scale, that can be used for clinical trials.
Media & Buffer Formulation, Optimization & Validation Developing the appropriate requirements for growing cells upstream (media) and preparing ingredients for downstream purification (buffers).
Master Product Stability Study Programming &amp Validation Product stability is obtained when purified material remains within specification during storage.
Formulation Chemistry Development Preparing a purified batch of material by combining chemical components in a specified manner.
Analytical Assay Development & Optimization An analytical assay is a method to qualitatively or quantitatively measuring the specific parameters of a product.
Raw Materials Selection & Validation The process of selecting and testing different components used in the manufacture of the product.
Process Validation Support Ensure a process that consistently produces a result or product that meets certain predetermined specifications.
Validation Services to Support Facilities/ Utilities/ Equipment Functions to ensure that facilities and equipment are operating within defined requirements.
Fill/ Finish Manufacturing Development Support Develop the process parameter range needed to fill and package a drug product to ensure it meets its final specifications.
Final Container Product Labeling & Packaging Support Placing the final label on the container and placing the container in its final package.
Analytical Assay Validation for Product Lot Release & Clinical Testing Confirm that the test methods for the final product are accurate and repeatable.
Product Stability Optimization Develop and evaluate modifications to product and/or processing steps to improve the product shelf life.
Lyophilization Development & Validation Develop the process to freeze dry products to improve shelf life and confirm the process consistently meets final specifications.
Commercial Scale Bulk Manufacturing Production of product (vaccines, biologics, etc) generally in larger scale batches.
Fill & Finish Manufacturing Filling and packaging of the formulated product into the final package.