Food and Drug Administration (FDA) Office of Clinical Pharmacology (OCP) – Multi-phase/Multi- site Clinical Studies and Laboratory Support Indefinite Delivery-Indefinite Quantity (IDIQ) Type Contract

General Information:

Document Type:                                 Sources Sought Notice (FDA-SSN-121190)

Release Date:                                      January 18, 2023

Response Date:                                   February 04, 2024 at 3.00 P.M. EST via e-mail to craig.wright@fda.hhs.gov

Contact Information:                     

Craig Wright
Contract Specialist
Office of Acquisition and Grants Services
U.S. Food and Drug Administration
Email: craig.wright@fda.hhs.gov

Description:  Food and Drug Administration (FDA) Office of Clinical Pharmacology (OCP) – Multi-phase/Multi- site Clinical Studies and Laboratory Support Indefinite Delivery-Indefinite Quantity (IDIQ) Type Contract

This is a Food and Drug Administration Small Business Sources Sought Notice for Commercial Services. This is NOT a solicitation for proposals, proposal abstracts, or quotations.

The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition, 541714, Research and Development in Biotechnology (except Nanobiotechnology), with a size standard of 1000 employees. The Product Service Code is AJ12, General Science and Technology R&D Services; General science and technology; Applied Research.

Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice.

**QUESTIONS WILL NOT BE ENTERTAINED AS A RESULT OF THIS NOTICE**

Background:

The United States Food and Drug Administration (FDA) has a mission to protect public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. In addition, FDA is responsible for facilitating innovations that make medicines more effective, safer, and more affordable. To accomplish these goals, FDA has stimulated advancement of regulatory science, which is defined as “the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all FDA regulated products.” FDA’s vision is to facilitate the integration of new science into the process of evaluating the safety and efficacy of proposed and marketed products and to close the gap between scientific innovation and this process of drug review. To achieve this vision, we perform mission-critical research to develop and evaluate tools, standards, and approaches to assess the safety, efficacy, quality, and performance of drugs.

The FDA has the need for Phase I-type clinical trial operations. Depending on the project, the clinical trials under this contract may include assessment of different drug and metabolite concentrations, biomarkers levels, or include novel experimental methodologies. The clinical trials may require enrollment of different subjects depending on the research topic (e.g. target populations may be healthy volunteers, demographic subsets of healthy volunteers, or subjects with conditions of interest) as well as allow for single or multiple dose administration of different drug or biologic products (e.g. small molecules, peptides, proteins or oligonucleotides). The clinical trials may also require multiple sites to ensure timely enrollment and study completion. All clinical trials shall be carried out in compliance with all FDA regulations and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines.

The FDA also requires execution of supportive laboratory studies related to bioanalytical/biomarker/omics (omics refers to range of techniques for characterization and quantification of biologic molecules). These assessments may be needed for samples collected from within the clinical trial or could be required as a standalone option for mission-critical needs. The results of studies and other performed work under this contract will be used to advance regulatory science.

Overall, the efforts would support a full range of services from clinical trial protocol development, clinical trial execution, conducting supportive laboratory studies, and bioanalytical/biomarker/omics services, where required.

Objectives:

The scope of activities FDA may require of the contractor shall include the capability to conduct multiple Phase I clinical trials within a year and at times in parallel, and the provision of a full range of services to support the clinical trials and reporting of the results. All clinical trials shall be carried out in a timely fashion and in compliance with all FDA regulations and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines.

The contractor should also be able to provide laboratory studies including bioanalytical/biomarker/omics support that includes determination of drug concentration, anti-drug antibodies, and multiple pharmacodynamic biomarkers. Any bioanalytical/biomarker work shall be carried out in a timely fashion. Unless otherwise specified, method validation shall be performed in compliance with FDA’s Bioanaytical Method Validation Guidance (https://www.fda.gov/media/70858/download). Sample analysis does not need to be performed under complete Good Laboratory Practice (GLP) guidelines.

Project Requirements:

Each task order may have its own scope of work. We present one example below to demonstrate how the Center for Drug Evaluation and Research (CDER) Office of Clinical Pharmacology (OCP) uses the contracted study mechanism to address concerns.

Example1. Clinical Study to Investigate the Urinary Excretion of N- nitrosodimethylamine (NDMA) after Ranitidine Administration

In September 2019, FDA received a citizen petition indicating that high levels of N-nitrosodimethylamine (NDMA), a probable human carcinogen,1 had been detected in specific lots of ranitidine.2 The petitioner also proposed that ranitidine could convert to NDMA in vivo by ranitidine releasing its dimethylamine (DMA) group, which could then be nitrosated to NDMA in the presence of nitrite. In response, FDA immediately alerted the public and initiated an investigation.

The FDA found that the analytical procedure used to quantify NDMA could convert ranitidine to NDMA under the high temperatures used. Thus, a new method using lower temperatures was developed and validated, which resulted in approximately 3000-fold lower NDMA amounts; however, many ranitidine products still contained NDMA at levels above the acceptable daily intake limit (96 ng/d). FDA has also conducted tests that simulate what happens to ranitidine after it has been exposed to acid in the stomach with a normal diet.  Results of these tests indicate that NDMA is not formed in typical stomach conditions.

Regarding potential in vivo conversion of ranitidine to NDMA, the primary evidence came from a 10-participant study that reported an approximately 400-fold increase in NDMA and an approximately 2.5-fold increase in DMA excreted in urine after oral ranitidine (150 mg). However, there were general study limitations (e.g., no randomization); no information on controlling for environmental or dietary exposure to nitrites, nitrates, or NDMA; and limited details on sample handling and validation of analytical methods, which used elevated temperatures. This level of increase is substantially greater than would be expected from laboratory testing.  Further evaluation is necessary to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may potentiate formation of NDMA in vivo.

In February 2020, a task order against an existing contract was issued to conduct a clinical study using a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels 24-hours after ranitidine administration in comparison to placebo when subjects are administered a low nitrite/NDMA meal and when subjects are administered a high nitrite/NDMA meal. This was accomplished through a randomized, placebo-controlled, single-dose, 4-period crossover study with 18 healthy subjects. Treatment arms are as follows with treatment arms A and B randomized for the first two periods and treatment arms C and D randomized for the last two periods.  Meals will be identical for arms A and B (low nitrite/NDMA meal) of the study and for arms C and D (high nitrite/NDMA meal):

A.        Ranitidine + low nitrite/NDMA meal;

B.        Placebo + low nitrite/NDMA meal;

C.        Ranitidine + high nitrite/NDMA meal;

D.        Placebo + high nitrite/NDMA meal.

Period of Performance:

The ordering period for this IDIQ Contract will be five (5) years. Performance under Task Orders (TOs) may extend beyond the five-year ordering period. Each TO will have its own Period of Performance.

Capabilities and Technical Experience:

Provide a capability statement describing how your company would be able to meet the requirements.

Business Status:

Please provide your business size status (e.g., small business, 8(a), HUBZone, etc.) and SAM.gov Unique Entity Identifier (UEI) number.

Disclaimer and Important Notes:

This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in SAM.gov. However, responses to this notice will not be considered adequate responses to a solicitation.

Responses to the sources sought shall be no longer than 10 pages.