FAQ

Production Assistance for Cellular Therapies (PACT) is an NHLBI-funded initiative that began in September 2003 to support manufacturing of cell therapy products for use in clinical trials. After a successful 6 years, PACT was renewed in January 2010 with an expanded scope which included providing translational services. August 2016 marked the third iteration of the PACT program initially focused on providing cell therapy products for IND-enabling pre-clinical studies, translational services support. PACT has recently expanded its scope to include clinical cell product manufacturing support for use in early phase clinical trials. PACT offers expertise in translational and clinical development and scale-up capability needed to produce cellular products under cGLP and cGMP/cGTP regulations. PACT also offers comprehensive regulatory services. PACT is experienced in preparing FDA INTERACT (pre-pre-IND) or pre-IND meeting packets and can provide a gap analysis for investigators to support a successful IND application.

No. PACT provides translational development services and cell product manufacturing to requesting investigators.

No. NHLBI provides funds only to the PACT facilities for cell therapy product manufacturing and translational development services support. These facilities were chosen based on their existing expertise. They will function as a contract manufacturing service to produce cellular products to any approved applicant. PACT does not conduct animal studies for requesting investigators. If your proposal includes an animal study, you are expected to have sufficient funding from non-PACT sources to procure resources and conduct your animal study, which will utilize the PACT-manufactured cell product.

Many grants have limited funding, especially for cell product optimization studies and IND-enabling studies. PACT can provide additional resources for these components of your project. This is accomplished through existing PACT manufacturing facilities using their infrastructure and NHLBI support to manufacture your cellular product. The PACT facilities have the expertise to ensure that your cellular product will meet current regulatory requirements and have experience in the manipulation of many cell types, removing some of the unknowns when approaching a new cell type.

Yes. PACT’s scope has been expanded to include cell product manufacturing for early phase clinical trials.

Investigators with scientifically meritorious and innovative ideas who do not possess the resources to manufacture cell products for GMP/GLP studies, relevant animal model testing or other IND-enabling studies at their own facilities are encouraged to apply to PACT. Investigators can request translational development services in addition to cell product manufacturing services. Investigators may also apply for regulatory services.

 

Yes. Small businesses that meet the criteria for NIH support may apply. This includes SBIR and STTR mechanisms.

No. You do not have to be affiliated with one of the PACT facilities to use PACT to produce your cellular product or receive regulatory services.

Yes. The main requesting investigator must be located in the US. However, it is possible for the requesting investigator to subsequently ship and provide a cellular product to a collaborating, non-US investigator. PACT was designed to provide manufacturing assistance and support for IND-enabling studies to approved requesting investigators within the United States in order to meet the US government FDA regulatory scope.

The following types of Request for Service Applications (RSAs) will be accepted:

   a. Regulatory assistance only (e.g., IND assistance, gap analysis, etc.)
   b. Translational development only (e.g., translational research development, scale-up)
   c. Clinical manufacturing only
   d. Regulatory assistance and translational development
   e. Regulatory assistance and clinical manufacturing

A Clinical RSA may include a limited amount of translational work (I.e., validation runs). Depending on the extent of translational work, the applicant may be directed to submit a Translational RSA first. After the translational work is complete, a Clinical RSA can be submitted.

NHLBI accepts applications involving cardiovascular repair and disease, lung repair and disease, hematologic disease and hematopoietic cell transplantation, outside of primary treatment for malignancy.

Investigators requesting cell products to be manufactured under cGMP/cGLP conditions for use in proof-of-principle, IND-enabling research and early phase clinical trials in heart, lung, blood and sleep indications will be considered by PACT.

PACT will consider conducting activities that will bring proof-of-concept discoveries into the translational development stage. These activities include scale-up, optimizing manufacturing processes, SOP development, CMC section development and cell product manufacturing for relevant animal model studies and other IND-enabling studies conducted by the requesting investigator. PACT requires scientific, technical, and logistic details required to manufacture the requested product.

For clinical applications, PACT requires that you position your product as intended for use in an early phase human clinical trial and that you supply evidence of sufficient and/or petitioned funding to support the clinical trial.

Other NIH Institutes may sponsor applications to utilize PACT services. Please consult with your program officer prior to initiating a PACT application. You will be asked to provide the program officer’s contact information in the application.

Please contact with questions about the application process.

Our website provides evaluation criteria guidance that we encourage you to review while completing your application. Translational applications will be evaluated using the following criteria:

Approach

• Overall project: Is the conceptual framework, design, methods, and analysis adequately developed, well integrated, and appropriate?

Preliminary Data

• Are the preliminary data sufficient to develop Standard Operation Procedures (SOP) for manufacturing?

Manufacturing Feasibility

• Do the reviewers foresee difficulties in manufacturing of this product?
• Are there obstacles that would prevent FDA approval?
• Is the application conducive for completion of translational development within 2 years?

Importance

• Does this application address a significant problem?
• If the aims (short term/preclinical studies and/or long term/clinical trials) are achieved, how will scientific knowledge be advanced?
• How will this application affect ideas, methods, technologies, treatments, or services that drive this field?
• Does the applicant provide a path to eventual clinical use?

Applicant

• Is/Are the applicant(s) and their collaborators, and other researchers well suited to the project?
• If the applicant(s) is/are in the early stages of independent careers, do they and their team have appropriate experience and training to see the preclinical project through to initiation of the clinical trial?
• If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?
• If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise that is appropriate for the project?

Innovation

• Is the project original and innovative? For example, does the application address an innovative hypothesis or critical barrier to progress in the field? Does the application develop or employ novel concepts, approaches, methodologies, tools, or technologies? If not innovative in nature, does the application possess a solid approach that is essential to the advancement of the field?  
• Is there likelihood that the proposed translational research will make substantial contributions to the cell-based therapy field?

Clinical applications will be evaluated using the following criteria:

Approach

• Overall project: Is the conceptual framework, design, methods, and analysis adequately developed, well integrated, and appropriate?
• Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested?

Significance

• Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, and based on previously well-designed preclinical and/or clinical research?

Manufacturing Feasibility

• Are the product specifications and characterization information adequate?
• Do you foresee difficulties in manufacturing of this product?
• Are there obstacles that would prevent FDA approval?

Importance

• Does this application address a significant problem?
• If the aims of the project are achieved, how will scientific knowledge and/or clinical practice be advanced?
• How will this application affect ideas, methods, technologies, treatments, or services that drive this field?  

Applicant

• Is/Are the applicant(s) and their collaborators, and other researchers well suited to the project?
• If the applicant(s) is/are in the early stages of independent careers, do they and their team have appropriate experience and training to see the initiation of the clinical trial?
• If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?
• If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise that is appropriate for the project?

Innovation

• Is the project original and innovative? For example, does the application address an innovative hypothesis or critical barrier to progress in the field? Does the application develop or employ novel concepts, approaches, methodologies, tools, or technologies? If not innovative in nature, does the application possess a solid approach that is essential to the advancement of the field?
• Is there likelihood that the proposed clinical trial will make substantial contributions to the cell-based therapy field?

Examples of projects supported by PACT include, but are not limited to, those listed below. These are examples only; applicants should not feel limited to the examples mentioned.

• Regulatory support for pre-IND and IND submissions, Chemistry, Manufacturing, and Controls (CMC) section development.
• Providing consultation on cell manufacturing, trial design, regulatory issues to prepare for implementation of early phase cell therapy trials.
• Transfer and optimize cell manufacturing protocols from pre-clinical laboratory to GMP clinical production methods.
• Produce cell products for use in relevant animal safety studies or clinical studies.  Examples include:
  • Providing genetically engineered cells for lung and sleep disorders such as narcolepsy and cystic fibrosis.
  • Providing mesenchymal stromal cells for heart and lung indications such as myocardial infarction, pulmonary arterial hypertension, and acute lung injury.
  • Providing cardiomyocytes derived from human embryonic stem cells for treatment of cardiovascular diseases.
  • Providing expanded lymphocyte subpopulations such as T regulatory cells or group 2 innate lymphoid cells to reduce Graft-versus-Host Disease after hematopoietic cell transplant.
• Developing purity/potency assays and other release criteria for cell products.
• Establishing GMP-compliant cell production standard operating procedures (SOPs).
• Providing centralized laboratory testing (e.g. flow cytometry panels, functional assays such as assessments of cell homing or migration) for assay standardization and cost consolidation.

The following lists examples that will not be supported through PACT:

• Cell product development for which efficacy in an animal model has not been demonstrated.
• Gene vector production. Investigators may refer to the for support of preclinical and clinical-grade vector production and other gene therapy related services.
• Cell processing involving only simple cell isolation such as cell selection or cell depletion of hematopoietic cells by established methods such as magnetic cell separation or density gradients.  

Below is a list of other alternative funding/supporting resources:

Access our website at www.pactgroup.net

• Click on ‘Apply to PACT’
• Registration is required to access the application system.
• Informational materials are available on the ‘Apply to PACT’ web page to assist you in completing the application.

Clinical and Translational applications undergo a two-part review process. An application is initially submitted for program scope review, which NHLBI will review and either approve or reject for full application submission. If approved for full application submission, requesting investigators can submit the full application at any time. Full applications received during the first week in a given month will be reviewed by an independent scientific review board (SRB) that same month. Full applications submitted after the first week in a given month will be reviewed the following month by the SRB. Additional questions or clarifications may be generated by this review. Once your application is approved, the NHLBI will solicit proposals via a Task Order Request for Proposal (TO-RFP) from the 5 PACT facilities. Interested PACT facilities will competitively bid to perform the work by submitting a task order proposal to NHLBI. NHLBI will evaluate proposals against the requirements of the TORFP and the Task Order will be awarded to a PACT facility in accordance with the requirements stated in the TO-RFP. After Task Order award, technical and material transfer agreements between the designated PACT facility and the requesting investigator’s institution/ organization will be negotiated. The requesting investigator will communicate directly with the PACT facility to finalize the services and production timeline. When both parties reach agreement, the project may begin.

Regulatory-only applications, unlike Clinical and Translational applications, only undergo NHLBI scope review and do not undergo the Task Order Request for Proposal (TO-RFP)/ Task Order process. Regulatory services are provided through the PACT Coordinating Center If approved, the PACT Coordinating Center will contact the investigator to commence regulatory services.

Requests for regulatory services in combination with translational development or clinical manufacturing services requests will also be accepted. For combination RSAs (Clinical/Regulatory OR Translational/Regulatory RSAs), the translational or clinical component of the RSA will undergo the two-part review process described above in parallel with NHLBI's review of the regulatory component of the RSA. Both components of the combination RSA will be reviewed and will be individually approved or not approved.

The overall timeline from the initial application for scope to initiation of work may take 4-6 months and depends on the timeliness of the requesting investigator’s responses and issuing and responding to TO-RFPs.  The timeline for a regulatory services-only requests will be less (approximately 1-2 months) since SRB review and Task Order Request for Proposal (TO-RFP)/ Task Order process are not conducted.

No. Applications may be submitted at any time and are reviewed on an on-going basis.

Yes. Investigators who have completed additional studies that address NHLBI’s comments may re-apply for PACT services. Such applications should include a statement describing in detail how the “new application” is different from the previous one.

PACT will take into consideration the project timeline when approving and supporting projects to minimize the possibility of projects going beyond the current PACT program contract. PACT is not able to commit to supporting projects that go beyond the current funding period of the PACT program. For projects that will extend beyond June 2021, investigators are advised to pursue alternate support, which can include PACT, should PACT be renewed, or work with their existing PACT facility to explore continued manufacturing and funding options. If the work is part of an RO1 or other NIH funding, investigators are encouraged to communicate with their program officials regarding continued support for cell manufacturing services.

Yes. Investigators receiving PACT services must agree to acknowledge PACT support in publications and presentations

Part of the PACT mission is to promote interest in cellular therapy/engineering among junior investigators and scientists in training, preparing them for careers in cellular therapy/ engineering. We host free web seminars aimed at sharing expertise and lessons learned in the PACT scope area. Click on the Education tab on our website at www.pactgroup.net for upcoming educational events and resources (slide presentations, audio recordings) from past PACT-sponsored educational activities.

PACT provides a collaborative development environment.  Any intellectual property that was developed prior to working with PACT contractors remains the property of the original owner. During the provision of PACT service, it is possible to co-develop intellectual property with the PACT contractors. If this occurs, the parties shall have joint ownership of the resulting intellectual property.

PACT will offer RMIP awardees technical and administrative services including regulatory assistance. Please refer to the for additional details and information.