A02 -RFI-GMP Manufactured ALF-551 14 Mar 24.pdf

REQUEST FOR INFORMATION (RFI)

1.0 RFI TITLE: Procurement of Good Manufacturing Practices (GMP) Manufactured ALF55

2.0 AGENCY: Walter Reed Army Institute of Research (WRAIR)

3.0 LOCATION: 503 Robert Grant Avenue, Silver Spring, MD 20910

4.0 SUBJECT: WRAIR is conducting market research to determine whether a commercial solution can provide the product for 2.75 liters of the compound Army Liposome Formulation (ALF) containing 55 mol% cholesterol

(ALF55).

5.0 DISCLAIMER: This is an RFI as defined in FAR 15.201(e) to ascertain whether a commercial item exists that provides the capabilities described herein.

This RFI is issued solely for information and planning purposes and does not constitute a solicitation. Neither unsolicited proposals nor any other kind of offers will be considered in response to this RFI. Responses to this notice are not offers and will not be accepted by the Government to form a binding contract. In keeping with the standards of FAR Part 10, the Government may request additional information from respondents. Respondents are solely responsible for all expenses associated with responding to this RFI or any follow-up information request. All information received in response to this RFI or any follow-up information request that is marked Proprietary will be handled accordingly. Responses to the RFI will not be returned. At this time, questions concerning the composition and requirements for a future request for proposal will not be entertained.

6.0 DESCRIPTION:

Specific Product Requirements:

• Product description: The ALF55 drug substance is defined as Army Liposome Formulation (ALF) containing 55 mol% cholesterol. It consists of liposomes containing dimyristoylphosphatidylcholine (DMPC), cholesterol (chol), dimyristoylphosphatidylglycerol (DMPG), and monophosphoryl 3-deacyl lipid A (3D-PHAD®) in a molar ratio of 9:12.2:1:0.11 (DMPC:chol:DMPG:3D-PHAD®).. All lipids used to manufacture ALF55 drug substance are synthetic. It shall be buffered in Sorenson’s buffered phosphate buffered saline, pH 6.2 (SPB).

• Quantity required: 2.75 Liters

• Product manufacturing requirements: All lipids used in the manufacture of ALF55 shall be synthetic and manufactured under cGMP conditions in compliance of 21 CFR parts 210 and 211. The manufacturing of ALF55 bulk consists of several steps: preparation of the lipid stocks in organic solvents, rotary evaporation of the ALF55 precursors, vacuum drying of ALF55 precursors, hydration of ALF55 intermediate using SPB, size reduction of ALF55 intermediate, and filtration of ALF55. The manufacturing of ALF55 shall be conducted under cGMP conditions in compliance with 21 CFR parts 210 and 211. The vendor shall accommodate an onsite audit and will need enter into a quality agreement with ORA and WRAIR. The manufacturing details shall be provided to ORA/WRAIR for inclusion in the ALFQ Master File on file with the FDA. Alternatively, the vendor shall provide a letter of cross-reference to their QS-21 Master File on file with the FDA.

• Product component details required: The ALF55 shall meet the following specifications:

The ALF55 drug substance is a liposome suspension. The molar ratio of the lipid constituents is 9:12.2:1:0.11 (DMPC:cholesterol:DMPG:3D-PHAD®).

The purpose of this RFI is to solicit information on the criteria or Specifications for GMP ALF55 as stated in the below table.

Test Proposed Acceptance Criteria Analytical Method Physical Examination Opalescent to white homogenous suspension Visual inspection

Liposome Particle Size Distribution 30-150 nm DLS Concentration:

Total PC (DMPC + Lyso PC)

27.76 ± 3.86 mM LC-MS/MS

Concentration:

Total PG (DMPG + Lyso PG)

2.87 ± 0.43 mM LC-MS/MS

Concentration:

Cholesterol

34.93 ± 5.24 mM LC-MS/MS or 1H NMR

Concentration:

3D-PHAD®

0.33 ± 0.05 mM LC-MS/MS

Identity: DMPC Rt and MW correspond to that of standard DPMC

LC-MS/MS

Identity: DMPG Rt and MW correspond to that of standard DPMG

LC-MS/MS

Identity: Cholesterol Rt and MW correspond to that of standard cholesterol

LC-MS/MS

Identity: 3D-PHAD® Rt and MW correspond to that of standard 3D-PHAD

LC-MS/MS

Impurities: Lysophospholipids Total lysophospholipid < 20% of phospholipid

LC-MS/MS

Impurities: 25-hydroxycholesterol < 5% of cholesterol LC-MS/MS Degradation Products of 3D-PHAD < 20% of 3D-PHAD® LC-MS/MS Microbial Examination of Non-Sterile Products

Aerobic Count <10 CFU/mL Yeast and Mold <10 CFU/mL

Microbial Enumeration Tests, USP <61>

Residual solvents < 50 ppm chloroform < 250 ppm all organic solvents total in the lipid

GC/FID

Microbial Examination of Non-Sterile Products

Absence of S. aureus, Salmonella, P.

aeruginosa, and E. coli

Specified Organism Tests, USP <62>

3D-PHAD = Monophosphoryl 3-Deacyl Lipid A; CFU= Colony Forming Unit; DLS = Dynamic Light Scattering;

DMPC = 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine/ Dimyristoyl phosphatidylcholine; DMPG = 1,2- Dimyristoyl-sn-Glycero-3-Phospho-(1’rac-Glycerol) (sodium salt)/ Dimyristoyl phosphatidylglycerol; GC/FID = Gas chromatography/Flame ionization detection; LC-MS/MS = Liquid Chromatography- Tandem Mass Spectrometry; USP= United States Pharmacopeia.

Specific Delivery Requirements:

• Packaging requirements: The ALF55 drug substance was filtered through a One-Touch® Assembly 5 L TepoFlex® Biocontainer and Filter Assemblies from Meissner Filtration Products. It should be stored at 2- 8⁰C under temperature monitored conditions. The ALF55 shall be shipped under temperature-controlled conditions with 2 temperature monitors.

The above is for information purposes only for a response to the RFI.

Industry partners may provide information on individual aspects of these requirements as partnering is encouraged to meet the total desired requirements.

7.0 SUBMISSION INSTRUCTIONS: Responses from all capable and qualified sources are encouraged to respond to this request. The subject header of the email for submission the RFI response shall be: “Procurement of GMP MANUFACTURED ALF55”. All information regarding capabilities statements or any other proprietary information relative to this RFI shall be marked appropriately.

White papers should adhere to the following formatting and outline instructions:

1. All submissions shall be made electronically and be in one of the following formats: Microsoft Word or Adobe PDF. There is a 20-page limit.

2. Cover Page (1 page)

A. Title

B. Organization

C. Respondent’s technical and administrative points of contact (names, addresses, phone numbers, and email addresses)

D. Topic area(s) addressed

3. Discuss the respondent’s ability to meet the following:

A. Quantity required: 2.75 Liters

B. Ability to meet specific requirements

C. Specific Delivery Requirements:

• Packaging requirements: Packaging requirements: The ALF55 drug substance was filtered through a One- Touch® Assembly 5 L TepoFlex® Biocontainer and Filter Assemblies from Meissner Filtration Products. It should be stored at 2-8⁰C under temperature monitored conditions. The ALF55 shall be shipped under temperature-controlled conditions with 2 temperature monitors.

• Delivery location:

Walter Reed Army Institute of Research (WRAIR) Pilot Bioproduction Facility (PBF) Forest Glen Annex, Building 501 Silver Spring, MD 20910

Please note that responses are due no later than 1200 PM ET, 22 March 2024. The preferred method of submission is via email. The point of contact for this action is Nathaniel Reus, Contract Specialist at nathaniel.a.reus.civ@health.mil

Only electronic responses are requested. No evaluation letters and/or results will be issued to the respondents. At this time no solicitation exists; therefore, please do not request a copy of the solicitation. NO PHONE CALLS PLEASE. It is the responsibility of any potential offeror to monitor this site for the release of any solicitation or synopsis.

mailto:nathaniel.a.reus.civ@health.mil

9.0 SUBMISSION CONTACT INFORMATION: Interested entities shall forward submissions to Nathaniel Reus, Contract Specialist at nathaniel.a.reus.civ@health.mil no later than the 1200 PM ET on 22 March 2024.

Telephonic communication will not be considered as submission nor receive response.

Responses shall be submitted via e-mail only. The font shall be Times New Roman, size 12, single space. All submissions become Government property and will not be returned.

10.0 REQUIRED INFORMATION: Fill in the below table when responding to this RFI.

Question Answer RFI Number Company Name Company Address Point of Contact Phone Number E-mail Address Tax Identification Number (TIN) CAGE Code DUNS Number Company Web Page Company Location(s) Company is / is not a Small Business Company is / is not SAM Registered Other Socio-Economic Classifications (e.g. 8(a), HUB Zone, Woman-Owned, Veteran-Owned, Service- Disabled Veteran-Owned)

If 8(a), date that the company graduates from the program

Has this item of supply been sold in substantial quantities in the commercial marketplace?

mailto:nathaniel.a.reus.civ@health.mil