1. PROJECT BACKGROUND & PURPOSE OF THE RFP

1.1 Background to project

There is a high burden of disease of neonatal sepsis globally but especially in LMICs. In 2018, WHO estimated 2.5 million deaths occurred in the neonatal period (0-1 month), mostly in LMICs. 15% of neonatal deaths were attributed to sepsis, infections being the third most common cause of neonatal deaths (2018: 400,000 neonatal deaths due to infection). The current WHO guidelines recommendations for treatment of neonatal sepsis are:

• First line – intravenous ampicillin (or benzyl penicillin) and gentamicin
• Second line– Intravenous cefotaxime or ceftriaxone
• Other commonly used antibiotics:
  •  Amikacin
  • Piperacillin/tazobactam
  • Meropenem

GARDP has assessed a number of off-patent antibiotics that have an established neonatal dose to identify those that could be taken forward into such a trial. The antibiotics identified that met the criteria to be taken forward into the clinical trial were fosfomycin, flomoxef, in combination with each other or amikacin.

GARDP as Sponsor, is collaborating with 2 partners (namely Medical Research Council Clinical Trials Unit (MRC) and St George’s University of London (SGUL)) for the conduct of the following clinical trial:

An open label randomised controlled trial comparing novel combination and currently used antibiotic regimens for the empiric treatment of neonatal sepsis with a run-in confirmatory pharmacokinetic phase (NeoSep1).

This clinical trial is divided in 2 parts:

• NeoSep 1 study part 1: PK and safety evaluation of fosfomycin and flomoxef when given as a novel combination regimen, together or with amikacin (Complete)
• NeoSep 1 study part 2: Open label parallel group randomised trial comparing combinations of fosfomycin, flomoxef and amikacin and multiple other antibiotic regimens.

The second part will be conducted in about 16 sites spread between Asia, and Africa and will enrol about 3000 neonates. The study will use a novel trial design, analogous to network meta-analysis, which allows sites to randomise different sub-populations of neonates across different sets of clinically relevant antibiotic regimens for their site and specific subpopulation, known as the Personalised Randomised Controlled Trial design (PRACTical)1. This design has no specific single standard of care arm – each neonate is randomised between a set of regimens relevant to that neonate, and these sets differ from neonate to neonate and site to site. Importantly, the specific regimens and neonatal sub-populations most relevant to that site would be determined individually by each site before site initiation. Sites are likely to differ based on many factors including locally prevalent pathogens, local resistance patterns, local patterns of clinical care (e.g. on site maternity facilities), established routine clinical practice and local guidelines. Second-line options will depend on first-line regimen received.

Information about the relative performance of the different regimens in the trial would then be combined across the network of regimens being compared, using direct randomised evidence and indirect evidence across the network, to answer questions including “Of these different regimens, which is the best treatment to recommend?” “What is the ranking of these different treatments?”. Ranking can be done for multiple outcomes, including efficacy, safety, resistance, and cost.

1Personalised randomised controlled trial designs-a new paradigm to define optimal treatments for carbapenem-resistant infections. Walker et al Lancet Infect Dis 2021 Jun;21(6):e175-e181. doi: 10.1016/S1473-3099(20)30791-X)

1.2 Purpose of RFP

The purpose of this RFP is to find a microbiology central laboratory that will centralize and analyse bacterial isolates collected during the neonatal sepsis study at 8 sites across Asia-Pacific region:

• Bangladesh (2 sites)
• India (3 sites)
• Pakistan (1 site)
• Malaysia (1 site)
• Vietnam (1 site)

The central laboratory activities include the supply of information for storage and shipment of the collected clinical isolates, biobanking and analyse the bacteria.

2. SCOPE OF WORK

2.1. Required regional microbiology laboratory services

The bacterial pathogens will be collected by local laboratories that will follow their routine clinical microbiology procedures. Isolates from each patient will be stored by local laboratories preferentially at -80°C. If the sites do not have a -80°C freezer, isolates will be stored at -20°C.

The regional laboratory will be responsible for:

1. Developing and finalizing the microbiology laboratory manual, in collaboration with GARDP and its partners
2. Setting up tracking system for isolates in alignment with NeoSep1 isolate identifiers using a reconciliation process on participant ID and the isolates received and the manifest completed by the site.
3. Coordinating and managing the transfer of isolates on a six monthly basis (this may need to be assessed on a case by case basis as it will be affected by recruitment rates and culture positivity rates from local laboratories) to regional laboratory for analysis including but not limited to:
   1. Sourcing and providing local laboratories with GARDP approved commercial ready-to-use microbanks that contain the cryopreservative solution and beads (for example: Prolab microbanks, Microbank™ – Pro Lab Diagnostics Inc (pro-lab.com)).
   2. Printing and providing local laboratories with GARDP approved labels with isolates identifiers (see point 2), shipping manifests, and all other documents as required for proper tracking of material shipment.
   3. Providing GARDP with country specific regulatory requirements for the shipment of samples,
   4. Ensuring shipment of isolates is performed in compliance with local regulations (and IATA guidelines)
   5. Providing copies of such documentation to GARDP
   6. Signing material transfer agreements as required by respective country regulatory authorities
4. Microbanking of isolates for at least 5 years, with the possibility of extension for an additional 2 years
5. Analysis of isolates:
   1. ID confirmation of the isolates on receipt
   2. Antibiotic Susceptibility test (AST) of selected antibiotics on a quarterly basis or as agreed with GARDP. There is the estimate of 4 clinical isolates per site per month.
   3. Perform whole genome sequence (WGS) and identification of molecular resistance mechanisms in a selected number of isolates
6. Communication with GARDP and partners
   1. Attendance at scheduled monthly meetings
   2. Ad hoc calls

2.2. Technical Specification

2.2.1.Confirmation of isolate species identification

Reconfirmation of the isolates at the species level should be performed by matrix-assisted laser desorption/ionization of flight mass spectrometry technique (MALDI-TOF).

2.2.2. Antibiotic susceptibility test (AST)

The minimal inhibitory concentrations (MIC) should be performed using the EUCAST broth microdilution reference method ISO 20776-1:2019 (equivalent to CLSI) one panel per isolate. As quality control (QC) strains, E. coli ATCC 25922 and E. coli NCTC 13353 (ESBL/CTXM) to be used. Interpretative clinical breakpoints should be done for both, the EUCAST and CLSI. Fosfomycin MIC testing should be done using agar dilution supplemented with D-Glucose 6 phosphate sodium salt, as recommended by EUCAST and CLSI. Overall, it is expected that the study will collect 500-600 isolates.

The following panel and range of antibiotics will be tested in triplicate. The need for the measurement of each sample as triplicate will be assessed on the annual basis: Antibiotic

3. CRITERIA FOR SELECTING SERVICE PROVIDERS

The decision to award any contract as a result of this RFP process will be based on Service provider’s responses and any subsequent negotiations or discussions. The decision-making process will consider the ability of each service provider to fulfil GARDP’s requirements as outlined within this RFP and the total cost of the offer.

Proposals will be assessed against the main following criteria but not limited to:

3.1. Technical criteria

Technical criteria will weight maximum 70% of the award decision and are composed of criteria such as technical expertise, project experience, team structure, project plan proposal, project management capabilities, client recommendations, values and cultural fit

3.2. Financial criteria

Financial criteria will weight minimum 30% of the award decision and are composed of criteria such as competitiveness and completeness of the offer, payment schedule based on deliverables, special discount for non for profit organization

3.3. Proposals evaluation and bid defense meeting

Based on a pre-aligned selection grid, GARDD selection committee will evaluation all written proposals to determine which service providers shall be invited to a virtual meeting with GARDP Selection committee.

The duration of each meeting will be around 1 hour, including follow-up questions and answers. Agenda and expectations/questions expected for the meeting will be shared together with the invitation to participate.

3.4. Value-add and Insight

Please list/describe any additional services that you feel would have benefit to GARDP and associated costs if any.

3.5. Data Privacy

GARDP is committed to protecting and respecting your privacy in compliance with the European General Data Protection Regulation (GDPR). Our Privacy Notice (Annex 3) sets out the basis on which the personal data collected from you, or that you provide to us, will be processed by us in connection with your relationship with at GARDP, as vendors, service providers or third parties. By responding to our RFP, you explicitly consent to our Data Privacy Notice and confirm your understanding on how your personal data will be stored and treated by GARDP.

If you are interested to participate, please send a request to: RFP_Procurement@gardp.org to receive complete documentation of this RFP

Due/closing date: January 30th 2025