Attachment 1_PWS_CDER-2026-135969.pdf

STATEMENT OF WORK

OCP/DARS Purchase of Human Hindbrain Organoids

Background

Drug-induced changes to respiratory function represent a critical safety concern across multiple drug classes and use scenarios. In the human brain, respiratory function is controlled by key regions in the hindbrain. This procurement is for human iPSC-derived hindbrain organoids to evaluate drug-induced neural circuit activities in vitro and how they relate to changes in respiratory function.

This procurement directly supports FDA's Roadmap to Reducing Animal Testing in Preclinical Safety Studies (April 2025) and the draft guidance on General Considerations for the Use of New Approach Methodologies in Drug Development (March 2026), both of which prioritize the development and integration of human-relevant NAMs to reduce reliance on animal testing while improving the predictive accuracy of preclinical safety assessment. To support this mission, the Division of Applied Regulatory Science (DARS) has designed research to use human hindbrain organoids to evaluate drug-induced changes to respiratory-relevant neural circuits. This effort will give the FDA experience to better understand context-of-use and limitations of the hindbrain organoids, and how the results may be used to support safety and efficacy assessment. This procurement is thus consistent with FDA's mission to protect and advance public health by ensuring drugs are safe and effective.

The procured human hindbrain organoids will be used for invitro 3D MEA recordings to enable network-level characterization of drug-induced perturbations to respiratory-relevant neural circuits that lie deep within the tissue.

OBJECTIVES

• The objective of this contract is to obtain human hindbrain organoids and all associated materials necessary for culture and evaluation of drug-induced neural circuit activities to enable in vitro research to study drug effects.

SCOPE

Purchase of human hindbrain organoids and all necessary cells, reagents, and consumables to run electrophysiology studies, delivered on predetermined schedule to the FDA; functional data obtained on from the same human hindbrain organoids to document network response to drugs known to impact respiratory function and batch-to-batch data reproducibility.

REQUIREMENTS

The vendor will provide human hindbrain organoids in 12 deliveries. The first delivery should 96 organoids in 96-well plate format; the remainder should be 48 organoids per delivery. The organoids must express genes known to be expressed in hindbrain tissue:

DBX1 (Developing Brain Homeobox 1), SLC17A6 (VGLUT2), TACR1 (NK1 Receptor), SST (Somatostatin), OPRM1 (μ-Opioid Receptor), KCNJ6 (GIRK2 Potassium Channel), ARRB2 (β-Arrestin-2), ADRA2A (α2A-Adrenergic Receptor), SLC6A2 (Norepinephrine Transporter/NET), NALCN (Sodium Leak Channel Protein), SCN8A (Nav1.6 Sodium Channel), and CACNA1H (Cav3.2 T-type Calcium Channel). The organoids should also have been demonstrated to be useful to obtain electrophysiological data.

DELIVERABLES / SPECIFIC TASKS

For human hindbrain organoids,

• Clearly states the deliverables required, the schedule for delivery, the quantities, and to whom they should be delivered (can be service or supply)

• Describes the delivery schedule in calendar days from the date of award

• Identifies the type of documentation (printed and electronic-such as manuals) to be provided, as well as those quality indicators desired by the Government.

TASKS

• Task 1 - Deliver the described human hindbrain organoids and all necessary culture materials per deliverable schedule to FDA White Oak Campus (10903 New Hampshire Avenue, Silver Spring, MD 20993) on a predetermined basis, beginning two months after award.

• Task 2 – Perform functional characterization to demonstrate organoid response to drugs known to affect regulatory functions and establish batch-to-batch reproducibility measures.

o Drugs to be tested: fentanyl + naloxone, xylazine + atipamezole, d-methamphetamine + doxapram/CX717, alprazolam + flumazenil. Drug concentrations will be informed by the FDA; drug solutions exposed to the organoids will be collected and shipped to the FDA for concentration verification.

o Deliverables include data (raw and analyzed), analysis files, and study reports.

Data and report for each drug pair (combination) should be delivered separately, within one month at the end of data acquisition.

o This service includes electronic data delivery and sample return to the FDA. This can be performed in parallel with Task 1. At this time, we do not have an estimated timeline, as the schedule will be determined through discussions with the vendor and the FDA. Delivery will occur within one month following the completion of each task/batch.

Deliverables Estimated

Quantity/Freque ncy

Review or Delivery Date

Task 1 batch 1 (for 1 month use 96 organoids) 1 2 months after award batch 2 (48 organoids)

(3-4 weeks as requested by the FDA) batch 3 (48 organoids)

(3-4 weeks as requested by the FDA) batch 4 (48 organoids)

(3-4 weeks as requested by the FDA) batch 5 (48 organoids)

(3-4 weeks as requested by the FDA)

Deliverables Estimated Quantity/Freque ncy

Review or Delivery Date batch 6 (48 organoids)

(3-4 weeks as requested by the FDA) batch 7 (48 organoids)

(3-4 weeks as requested by the FDA) batch 8 (48 organoids)

(3-4 weeks as requested by the FDA) batch 9 (48 organoids)

(3-4 weeks as requested by the FDA) batch 10 (48 organoids)

(3-4 weeks as requested by the FDA) batch 11 (48 organoids)

(3-4 weeks as requested by the FDA) batch 12 (48 organoids)

(3-4 weeks as requested by the FDA)

Deliverables Task 2 Fentanyl + naloxone, 4 batches of organoids

4, at end of each batch completion

TBD,

approximately within 1 month of batch completion xylazine + atipamezole, 4 batches of organoids d-methamphetamine + doxapram / CX717, 4 batches of organoids alprazolam + flumazenil, 4 batches of organoids After steady state drug effect, attempt to reverse to demonstrate receptors responsible;

drug solutions exposed to the organoids need to be collected and shipped to the FDA for concentration verification.

• Delivery to:

US Food and Drug Administration Attn: Jun Zhao 10903 New Hampshire Ave, WO 64 Rm 2069 Silver Spring MD 20993

Vendor will contact the Project Officer: Wendy Wu (wendy.wu@fda.hhs.gov) / (301)796- 0081 and researcher: Jun Zhao (jun.zhao1@fda.hhs.gov, 301-250-6360) by phone or email to schedule first delivery within 7 days of the award date.

Deliveries must be coordinated with the Project Officer and/or researcher prior to shipment. No deliveries will be accepted without prior authorization from the Project Officer.

Vendor must notify recipient via email with tracking information when it is shipped.

Government Furnished Equipment (GFE)/ Government Furnished Information (GFI)

• NA – no government furnished equipment is required

Place of Performance

• All items are to be delivered to FDA’s White Oak Campus (10903 New Hampshire Avenue, Silver Spring, Bldg 64, Rm 2069, Silver Spring, MD 20993; Attn: Jun Zhao).

• Functional characterization to be conducted in offeror’s laboratories.

• Data and study report should be submitted to the FDA project officer and researcher via email; drug solution samples applied to the organoids to assess functional changes will be delivered to the FDA White Oak Campus (address shown above).

Period of Performance

• Eighteen (18) months from date of award for all deliveries to be completed.

Inspection and Acceptance Criteria

The Government will review all reporting requirement deliverables in accordance with specifications and standards identified in the statement of work or any directives issued by the COR. The contractor shall submit the reporting Requirements/Deliverables to the COR in accordance with the delivery schedule. The COR will perform inspection and acceptance of materials and services provided in accordance with the criteria stated in Attachment 2, Quality Assurance Surveillance Plan, and established in the detailed requirements specifications. The Contractor shall implement necessary changes within 10 business days from the day of change notification.