Vendor Response Form_75N95023R00004.docx

Notice ID: 75N95023R00004

VENDOR RESPONSE FORM

Title: Pharmacology Studies and Animal Model Development and Related Services for Drug Development Notice ID: 75N95021R00034

The Government seeks to obtain information about industry capabilities to support the DPI drug development programs by providing pharmacology studies and animal model development and related services for drug development. This requires novel, re-developed, optimized, or use of existing, validated animal models to conduct in vivo pharmacology studies, often for rare disorders and neglected diseases. These models are not able to be pre-determined as needs change depending on the disease; as such, access to both small (e.g., mice, rat) and large (e.g., dog, cat, monkey, pig) models are needed. In addition, therapies can cover a wide range of modalities such as, small molecules, and biologics (e.g. antibody, proteins, and cell and gene therapy).

Specifically, the Government seeks to determine industry capability in the following five areas:

1. In Vivo Pharmacology Services in Small Animal Models

2. In Vivo Pharmacology Services in Large, Non-Traditional Animal Models Including Non-Human Primates

3. Small Animal Models—Acquisition, Optimization/Refinement, and Development

4. Large, Non-Traditional Animal Models—Acquisition, Optimization/Refinement, and Development

5. In Vitro Pharmacology Studies in Ex-Vivo Tissue, Cell-Based or Other Relevant Animal Replacement Models including Acquisition, Optimization/Refinement, or Development of Such Relevant Experimental Model Systems

This response form has three parts – Part 1: Vendor Information, Part 2: Capability Matrices, and Part 3: Questions.

PART 1: VENDOR INFORMATION

Vendor Name:

Vendor Unique Entity Identifier (UEI):

Vendor Point of Contact (name and email):

PART 2: CAPABILITY MATRICES

Please indicate whether you have the capability to perform the sample activities listed by writing Yes or No in the applicable boxes.

(Y/N)

Defining pharmacokinetic/pharmacodynamic (PK/PD) relationships

Evaluating a range of endpoints and biomarkers in response to therapeutic candidates

Determining correct route of administration (e.g. SC, IV, PO, IT, or ICV)

Determining appropriate dosing parameters

Determining appropriate formulation(s) for administration

Examination of preliminary toxicity and safety parameters

Defining pharmacokinetic/pharmacodynamic (PK/PD) relationships

Evaluating a range of endpoints and biomarkers in response to therapeutic candidates

Determining correct route of administration (e.g. SC, IV, PO, IT, or ICV)

Determining appropriate dosing parameters

Determining appropriate formulation(s) for administration

Examination of preliminary toxicity and safety parameters

Developing novel or similarly existing genetically modified animals that are organ system specific or whole-body targeted for stable or conditional knock-ins, knock-outs, knock-downs, overexpression etc. using appropriate genomic techniques

· Generating targeting constructs per model requirement, e.g. plasmid DNA vector, single-stranded oligodeoxynucleotides (ssODNs), ribonucleic acid interference (RNAi) e.g. silencing ribonucleic acid (siRNA) or short hairpin RNA (shRNA)

· Use of cre-lox or tetracycline-induced technology as per model requirement

· Use of random DNA transgenesis or optimization of other delivery / gene editing system e.g. CRISPR/Cas9 or recombinant adeno-associated viruses (rAAVs)-mediated or other applicable technology per model requirement

· Transfection or electroporation of appropriate cells, e.g. skin fibroblasts (somatic) or embryonic stem (ES) cells with targeting construct with appropriate gene/editing delivery system(s) per model requirement

· Conducting somatic cell nuclear transfer (SCNT) into oocytes, transgene pronuclear microinjection or ES cell microinjection into fertilized eggs for uterine implantation to generate required fetuses / harvest appropriate cells for downstream procedures as necessary including genetic characterization

· Cryopreservation of embryos or sperm or harvested fibroblast for SCNT to resuscitate model as needed for future studies

Chemically or diet-induced models, e.g. CNS or respiratory or metabolic

Physiologically (procedure) induced models. e.g. anemic

Mechanically-induced models

Single or multiple genetic crossings / breeding

Re-derivation, back-crossing etc. as necessary to optimize or refine existing models if feasible and cost-effective

Production of live animals for phenotypic characterization / validation of model as well to support therapeutic discovery or development

Developing novel or similarly existing genetically modified animals that are organ system specific or whole-body targeted for stable or conditional knock-ins, knock-outs, knock-downs, overexpression etc. using appropriate genomic techniques, such as:

· Generating targeting constructs per model requirement, e.g. plasmid DNA vector, single-stranded oligodeoxynucleotides (ssODNs), ribonucleic acid interference (RNAi) e.g. silencing ribonucleic acid (siRNA) or short hairpin RNA (shRNA)

· Use of cre-lox or tetracycline-induced technology as per model requirement

· Use of random DNA transgenesis or optimization of other delivery / gene editing system e.g. CRISPR/Cas9 or recombinant adeno-associated viruses (rAAVs)-mediated or other applicable technology per model requirement

· Transfection or electroporation of appropriate cells, e.g. skin fibroblasts (somatic) or embryonic stem (ES) cells with targeting construct with appropriate gene/editing delivery system(s) per model requirement

· Conducting somatic cell nuclear transfer (SCNT) into oocytes, transgene pronuclear microinjection or ES cell microinjection into fertilized eggs for uterine implantation to generate required fetuses / harvest appropriate cells for downstream procedures as necessary including genetic characterization

· Cryopreservation of embryos or sperm or harvested fibroblast for SCNT to resuscitate model as needed for future studies

Chemically or diet-induced models, e.g. CNS or respiratory or metabolic

Physiologically (procedure) induced models. e.g. anemic

Mechanically-induced models

Single or multiple genetic crossings / breeding

Re-derivation, back-crossing etc. as necessary to optimize or refine existing models if feasible and cost-effective

Production of live animals for phenotypic characterization / validation of model as well to support therapeutic discovery or development

In vitro / ex-vivo cell/tissue-based model development activities:

· Stably (immortalized) or transiently transfected genetically modified cell lines e.g knock-in; knock-down, knock-out, overexpressing transgene

· Unaffected or affected donor-derived cells (e.g. induced pluripotent stem cells (IPSCs) or progenitor or primary cells from patients or animal models)

· Tissue-chip technology, e.g. single or interconnected organ systems

· 3D-cell tissue models e.g. skin, liver, neuronal architecture

· Freshly harvested tissue / cells

In vitro / ex-vivo cell/tissue-based study activities:

· Optimize conditions/ perform cell or tissue culture maintenance

· Compound treatment and collection of samples

· Assessment of cell viability / toxicity

· Relevant assaying of samples, e.g. fluid based, imaging etc.

PART 3: QUESTIONS

(Please note: these questions are for market research purposes only. Responses will be used for acquisition planning and will not impact future eligibility. Any mandatory qualification criteria will be included in the resultant solicitation, if issued, and must be met in accordance with the terms of the solicitation)

1. Vendors must have an approved Animal Welfare Assurance from the Office of Laboratory Animal Welfare (OLAW) at the NIH to perform work involving live vertebrate animals under an NIH contract. Do you currently possess an active OLAW Animal Welfare Assurance?

2. Vendors must be accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International to perform work involving live vertebrate animals under an NIH contract. Do you currently possess AAALAC accreditation?

3. Are there any animals you do not have the capability to work with?

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