PACT Services

The PACT program facilitates the transition of laboratory research developments into clinical research products for use in regenerative medicine as well as the novel treatments for cardiac, pulmonary, and blood diseases, the diseases under the auspices of the NHLBI. PACT supports translational research of novel cell therapies across several disease areas (i.e., beyond cardiac, pulmonary, and blood) in order to enable translational science research to reach the clinical trial stage.

PACT provides translational services as well as regulatory services in support of IND filing.

Vertical Tabs

Translational Research/Development

PACT will consider supporting activities that will bring proof of concept discoveries into the translational development stage. At the translational research and development stage, the goal is to define the desired characteristics of the cellular product, establish possible methods of cell isolation/expansion, and identify available cGMP reagents. In addition, it is the time where the results of toxicology and ‘proof of concept’ studies, including studies of cell survival kinetics and distribution, are reviewed and the findings extrapolated to human efficacy and safety profiles. Once the proposed cellular product is shown to have the desired activity and safety profile, clinical application may be considered. Tasks in translational development include the following:

  • Product characterization
  • Assay development
  • Standardization of manufacturing procedures
  • Scale-up procedures for cell manufacturing
  • Equipment validation
  • Customization of reagents
  • Product shipping validation
  • Preclinical toxicity and safety studies
  • Product specifications
Cell Manufacturing for Pre-clinical Animal Studies

PACT provides research grade and clinical grade cell product manufacturing to investigators to assist with in vivo and in vitro studies for preclinical studies involving relevant animal models. PACT may assist investigators with:

  • Animal model selection (i.e., normal, induced and spontaneous models of disease, gene knockout and transgenic)
  • Safety and toxicity studies
  • Dose level and frequency justification
  • Cell delivery route and device evaluation
  • Stability of the test product under the conditions of use
Process Development/Product Scale-up

A carefully designed and controlled process development system addresses product safety, efficacy, reproducibility, and manufacturing scale up. A critical review of the manufacturing process and all the materials and reagents involved in the production steps is required to avoid potential product quality and safety issues. PACT cell processing facilities (CPF) are experienced in the development of reproducible, large-scale methodologies, and are well acquainted with equipment and reagent qualification steps, as well as specific testing requirements when clinical grade reagents are not available.

Products approved by the program team for manufacture will be produced by the designated CPF according to the applicable regulatory requirements. The CPF contracted to manufacture the cellular therapeutic product will be determined based on the experience and expertise at the CPF and the production workload at each CPF. The CPF will assist the approved investigator with refining project work plans and timelines for his/her project.

Process Validation, SOP Development/Batch Production Records

Process validation is based on written procedures, and is thoroughly exercised to establish that the procedure can be performed as specified. This requires the development of standard operating procedures (SOP) for production and quality control (QC) testing as well as the identification of limits for various steps in production, criteria for acceptable starting material, and final product specifications. Once the production method and list of reagents have been finalized, the batch production record (BPR) is developed. This stage culminates with a series of validation runs to ensure the reproducibility of the process that results in a satisfactory product.

PACT cell processing facilities (CPF) have established written procedures and policies addressing all appropriate aspects of processing, testing, storage, distribution, quality control, and administration of cell therapy products. Each PACT CPF is responsible for documenting its own validation procedures and quality program effort. PACT provides support in the translation of laboratory protocols to clinical grade large scale manufacturing SOPs under the provision of a controlled good tissue practice (GTP) and good manufacturing practice (GMP) infrastructure. PACT will consider providing support in:

  • Optimizing manufacturing processes
  • SOP development
  • Establishment of product release specifications
  • CMC section development
Product Shipment

The PACT cell processing facilities (CPF) are well equipped and experienced in shipping cellular products to investigator sites. The PACT facilities have established procedures for the storage, distribution, and transport of materials, in-process and final products. Cellular products can be shipped in a validated liquid nitrogen dry shipper, on dry ice, or at ambient temperature as the product may require, in a validated, insulated container accompanied by a continuous temperature logger. Product shipment will contain a copy of the product Certificate of Analysis, a batch record summary and a confirmation of receipt form that must be completed and returned to the PACT CPF.

Technology Transfer

Technology transfer is a critical step in process development and has become a common practice among the PACT cell processing facilities (CPF) and investigators utilizing PACT services. It provides a mechanism to exchange ideas and enhance skills to further along cell therapy product development. Collaboration between the investigator and the PACT CPF facilitates the improvement of technical standards (i.e. assays, procedures, and reference standards), product design characterization, manufacture and the standardization of protocols, operating procedures, and processes for several cell types to streamline the translation of cell based therapies. PACT is aware of the need to protect the proprietary interests of academic/industry partners without compromising fundamental principles. PACT will provide product manufacturing and translational services to investigators, at different stages of development where related information may be considered confidential and/or proprietary. Confidentiality and intellectual property considerations are reviewed and discussed with approved investigators at the contract negotiation stage.

PACT-supported Regulatory Services

PACT is experienced in preparing INTERACT (INitial Targeted Engagement for Regulatory Advice on CBER ProducTs) (formerly pre-pre-IND; pre-IND) meeting packets; original IND submissions and subsequent IND amendments and Chemistry, Manufacturing and Controls (CMC).

PACT can provide a gap analysis for investigators in need of insight as to additional work that may be needed to support a successful IND application. The analysis will be geared toward an understanding of how the data generated from proof of concept, non-clinical and CMC development map to the requirements of an IND application. The gap analysis may cover the following areas, as needed:

  • Nonclinical studies to support the proposed clinical development plan
  • Manufacturing process for both nonclinical and clinical trial materials
  • Process development and scale up
  • Process validation
  • SOP development and batch production records
  • Product cryopreservation / labeling / release / shipment
  • Technology transfer
  • Regulatory finalization and IND submission assistance
  • Phase I and clinical development plan
  • FDA communications and commitments

Investigators also seeking to complete a PACT request for service application (RSA) for manufacturing or other translational services in parallel to regulatory services may also receive recommendations for facilitating a successful RSA as part of the gap analysis.

PACT can provide technical and administrative services to requesting investigators with IND applications and submissions. Periodic communications/meetings between a sponsor and FDA are conducted to resolve questions and issues prior to filing an IND, and occasionally throughout the course of a clinical investigation and product development as warranted by issues and events. PACT can assist investigators new to the IND submission process by navigating through and interpreting regulatory guidance documents in preparation of early stages of the IND application and provide consultation for and support with FDA interactions.

Clinical Study Protocol Development

Statistical and technical information regarding clinical study design, implementation, and monitoring will be prepared and presented to agency officials with the assistance of the PACT cell processing facility staff in collaboration with the investigator/IND sponsor as appropriate; however, the main contribution to the clinical study protocol will be in the form of investigational product information.