Subject:   Sample Testing of Good Manufacturing Practices (GMP) Materials for Walter Reed Army Institute of Research (WRAIR), Pilot Bioproduction Facility (PBF)

THIS IS NOT A REQUEST FOR PROPOSALS (RFP) OR A REQUEST FOR QUOTATIONS (RFQ); IT IS STRICTLY A REQUEST FOR INFORMATION (RFI). NEITHER UNSOLICITED PROPOSALS NOR ANY OTHER KINDS OF OFFERS WILL BE CONSIDERED IN RESPONSE TO THIS RFI. NO CONTRACT WILL BE AWARDED PURSUANT TO THIS ANNOUNCEMENT.

1.0  DISCLAIMER: 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. Responders are solely responsible for all expenses associated with responding to this RFI. All information received in response to this RFI 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 RFP will not be entertained.

2.0 SUBJECT:  The purpose of this requirement is to support the PBF’s testing of cell banks, bulk harvest materials, drug substance and drug products. The requirement is for complete testing of PBF supplied samples and provide completed Quality Assurance reviewed test reports to support the product release and stability testing of GMP materials for use in early phase (1/2a) clinical trials.

The testing is in accordance with 21 CFR Part 211 regulations for bulk cell harvest material,  Drug Substance (DS) release, Drug Product (DP) release, Master Cell Bank (MCB) and Working Cell Bank (WCB) release testing, DS stability, and DP stability. Products will include, but are not limited to, recombinant protein products produced from microbial, yeast or mammalian cell cultures, live attenuated virus, purified inactivated virus, bacteriophage, and monoclonal antibodies. Products will be BSL-1 or BSL-2.

3.0 BACKGROUND: The Pilot Bioproduction Facility (PBF) conducts research, development, production, and testing of vaccines and other biological products.  The PBF mission is to provide cost effective solutions to the DoD as well as other Governmental and external partners to advance research and development products into pilot scale manufacturing for early phase clinical trials. Production is performed, and products are tested, in compliance with current Good Manufacturing Practices (cGMP). Production is pilot-scale: 500 – 20,000 doses per finished lot of product and products are released for use in Phase I - II clinical studies under Investigational New Drug (IND) applications.  Vaccines being produced include, but are not limited to, those for prophylaxis against shigellosis, meningitis, malaria, dengue fever, zika, SARS-CoV2. Conventional as well as recombinant and other genetically engineered vaccines are undergoing development and production at WRAIR. Other types of biological products (i.e. therapeutics) are capable of being produced as well under the right circumstances.

4.0 RESPONSE INSTRUCTIONS:   Respondents should address the following in their capabilities statement:   

4.1. Testing Requirements

The contractor shall provide both standard and expedited testing options for the following:

4.1.1.Product Assays

• BCA Protein Content Assay
• microBCA Protein Content Assay
• Bradford Protein Content Assay
• Gravimetric Protein Content Assay
• A280 Protein Concentration
• Purity (DNA) A260/A280
• Purity (protein/aggregation) by Size Exclusion (SEC)
• Purity by Gel Electrophoresis (Reduced/Non-Reduced)
• Charge Heterogeneity by Capillary Isoelectric Focusing
• Capillary Zone Electrophoresis
• Mouse potency assay
• IFU Assay (S. Wang J Immunological Methods 324 (2007) 84-91)- Potency
• PFU Assay HPLC - Content
• Western blot identification assay - Identity
• Western blot expression assay- Potency
• Octet based antigenicity assay- Potency
• Adenovirus transgene potency assay
• Replication Competent Adenovirus (RCA) Assay
• Carbohydrate profile analysis by NPLC
• Free thiol
• Peptide mapping by RPLC
• Peptide mapping by RPLC-MS
• Mass spectrometry: Intact molecular weight determination (R/NR)
• Mass spectrometry: disulfide bond mapping analysis
• Mass spectrometry: carbohydrate analysis (occupancy and ID)
• Karl Fisher Moisture Analysis
• Amino Acid Analysis
• Southern blot
• pH
• TEM
• Edman degradation
• NextGen Sequencing
• Conductivity
• Osmolality and Osmolarity Determination
• qPCR target gene Identity/ Clearance assay (client supplied primer/probe)
• DLS
• Sucrose content
• Citrate content
• Phosphate content
• Arginine content
• Tween 20 content
• Tween 80 content
• Triton X content
• Subvis particles USP<787>
• Fill volume (Extractable volume)
• Container closure integrity
• Experimental Determination of Extinction Coefficient
• Determination of Zeta potential
• Barcode of Life Analysis (CO1 Barcode Assay)

4.1.2. Process Residuals

• Residual Benzonase
• Residual Kanamycin
• Residual Streptomycin
• Residual Gentamycin
• Residual Acetonitrile
• Residual Dichloromethane
• Residual N,N-Dimethoxyacetamide
• Residual N,N-Dimethylformamide
• Residual Methanol
• Residual Methylcyclohexane
• Residual DMSO
• Residual Formaldehyde
• Residual Formalin
• Residual huEGF
• Residual copper peroxide
• Residual H2O2
• Residual heavy metals by ICP-MS: Copper
• Residual heavy metals by ICP-MS: Zinc
• Residual Maleimide
• Residual Protein A
• Residual cyclohexamide
• Residual Hapten
• Residual tetanus toxoid
• Residual MTX
• Residual MZ

4.1.3. Host Reisduals

• Quantitation of Residual Host Cell DNA by qPCR - Vero
• Quantitation of Residual Host Cell DNA by qPCR - McCoy
• Quantitation of Residual Host Cell DNA by qPCR - HEK
• Quantitation of Residual Host Cell DNA by qPCR - CHO
• Quantitation of Residual Host Cell DNA by qPCR – E. Coli
• Quantitation of Residual Host Cell Protein by ELISA – Vero
• Quantitation of Residual Host Cell Protein by ELISA - McCoy
• Quantitation of Residual Host Cell Protein by ELISA - HEK
• Quantitation of Residual Host Cell Protein by ELISA - CHO
• Quantitation of Residual Host Cell Protein by ELISA – E. Coli
• Large format 2D PAGE Western – evaluation of HCP reagent coverage, product specific
• Proteomics analysis of host cell protein population, per sample (clearance study)

4.1.4. Safety/General:

• Endotoxin
• Murine retrovirus, extended Mink S+L Assay
• MAP: LCMV Challenged
• PCR for LCMV virus
• 14 Day Assay for the Detection of Adventious Viral Contaminants in Test Article Material
• Client Specific 28-day In Vitro Virus Assay for the Presence of Viral Contaminants, (3 cells lines)
• Adeno-Associated Virus (AAV) Serotypes 1, 2, 3, 3B, 4 and 6 by PCR
• BSA Detection and quantitation by Immunoassay
• HSA Detection and quantitation by Immunoassay
• Bovine 9CFR In Vitro Assay for 7 Viruses
• Porcine Mod. 9CFR In Vitro Viruses Assay
• Bovine Polyoma Virus (BPyV) Detection by PCR (Fluorescent Endpoint)
• Cell Line Identification of Chinese Hamster, Human, Mouse, African Green Monkey (Vero), Syrian Hamster (BHK), Porcine, Rat and Duck
• Human adventitious agent testing by RT-PCR
• Human Polyoma Virus BKV and JCV Detection by PCR
• Isolator Sterility Testing Using a Direct Inoculation Method (1 vial) (batch cost 40 samples)
• Isolator Sterility Testing Using a Membrane Filtration Method (batch cost 2-40 vials)
• Sterility Isolator Method Suitability Testing Using a Direct Inoculation Method (batch cost 40 samples)
• Sterility Isolator Method Suitability Testing Using a Membrane Filtration Method (Setup + 2 or More Samples)
• Microbial Limit with Direct Inoculation, GLP, MLT w/o Stasis
• Microbial Limit with Direct Inoculation, GLP, MLT with Stasis
• Microbial Limit with Membrane Filtration, GLP, MLT w/o Stasis
• Microbial Limit with Membrane Filtration, GLP, MLT with Stasis
• Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests using a Membrane Filtration Method (2-25 Samples in Batch)
• Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests using a Spread Plate Method - Enumeration Only (1 Sample)
• Microbiological Examination of Non-Sterile Products: Qualification of Microbial Enumeration Tests Using a Spread Plate Method
• Microbiological Examination of Non-Sterile Products: Qualification of Microbial Enumeration Tests using a Membrane Filtration Method
• Mycobacteria Assay, Low Bioburden
• Mycobacteria Assay, No Bioburden
• Mycobacteria, No Bioburden, Qualification Study
• Test for presence of Agar-Cultivable and Non-agar Cultivable Mycoplasma without Avian Controls (USP, EP, 1993 PTC)
• Mycoplasma by PCR
• Qualification of the Test Article for the Detection of Agar- Cultivable Mycoplasma in accordance with USP/EP/PTC/JP Requirements (Without Avian Controls)
• Qualitative Polymerase Chain Reaction Assay (PCR) for the Detection of Porcine Circovirus Type 1 and 2, GMP
• Quantitative Product Enhanced Reverse Transcriptase (QPERT) Assay for the Detection of Retrovirus in Biological Samples (1 Sample) - GMP
• Simian Foamy Virus (SFV) Detection by PCR
• Simian Immunodeficiency Virus Mac (SIVmac) Detection by PCR
• Simian Retrovirus Types 1 and 2 Detection by PCR (Fluorescent Endpoint)
• Simian T-Lymphotropic Virus (STLV) Detection by PCR
• Antibiotic resistance: viable cell count (WCB)
• Antibiotic resistance: expression stability (WCB)

4.2. Quality Requirements

4.2.1. Contractor shall perform GMP testing according to FDA regulations as established in 21 CFR Part 211

4.2.2. The Contractor shall utilize electronic records and signatures that comply with 21 CFR part 11

4.2.3. Contractor shall permit an annual audit of their Quality Systems for 2-4 people for 2 days. Items to be audited will include, but are not limited to:

• Documentation
• Raw data from previous tests
• Organization structure
• Policies on Out of Specification (OOS)
• Good Documentation Practices
• Equipment calibration and preventive maintenance
• Training records

4.2.4. Contractor shall utilize validated, monitored and alarmed controlled temperature equipment

4.2.5. The Contractor shall provide a change control plan outlining procedures for notification regarding the following:

• major changes to organizational structure;
• changes to Standard Operating Procedures;
• changes to the validation of a test

4.2.6.  The contractor shall maintain isolates recovered during sterility testing and residual virus assays for 90 days after recovery or 30 days after notice to the PBF, whichever is longer, and provide upon request

4.2.7.  The contractor shall alert the PBF if any situations are detected which would call into question previously reported results

4.3.       Out of Specifications (OOS) Events and Deviations

4.3.1.   The contractor shall handle OOS samples consistent with FDA guidelines

4.3.2.   The contractor shall alert the PBF within two business days of invalid assays that require repeating. A second retest is not approved without discussion and authorizaton

4.3.3.   The contractor shall alert the PBF within 2 business days of a confirmed OOS event

4.3.4.   The contractor shall hold OOS samples for a minimum of 30 days or until a definitive outcome has been obtained

4.3.5.   The Contractor shall notify the PBF within 2 business days regarding major deviations

4.3.6.   The Contractor shall notify the PBF within 2 business days regarding out of calibration notices affecting equipment used for completed testing

4.4. Stability 

4.4.1. The contractor shall adhere to stability timelines (testing shall be completed within +/- 2 weeks from assigned stability date)

4.5. Customer Service

4.5.1. The Contractor shall provide a dedicated program manager (PM) to serve as primary point of contact for all tests requested by the PBF

4.5.2. The Contractor shall provide a customer service line during normal business hours to provide information regarding testing status

4.5.3. The Contractor shall utilize a web-interface for sample test submission and Certificate of Analysis (CoA) retrieval

4.5.4. The Contractor shall provide anticipated result date at the time of test assignment

4.6. Documentation

4.6.1. The Contractor shall provide a list of all available tests including required sample volume, average turn-around time and expedited turn-around time (Deliverable)

4.6.2. The Contractor shall provide SOP documents upon request and have readily available for retrieval

4.6.3. The contractor shall provide assay qualification summaries upon request

4.6.4. The contractor shall provide instrument qualification summaries upon request

4.6.5. The contractor shall provide quality reviewed data with test reports

4.6.5. The contractor shall indicate on the test report whether test conforms to USP when applicable

5.0 RESPONSE INSTRUCTIONS:   Respondents should address the following in their capabilities statement:  

The capablities of performing the tasks requirements listed above.

The Contractor shall also provide their business size based on the NAICS identified in this RFI.

The Contractor shall also provide a list of contract awards references for similar or like work.

6.0 CONTACT INFORMATION:  All information regarding Capabilities Statements or any other proprietary information relative to this RFI shall be submitted via email to [email protected] no later than 2:00 p.m. E.S.T. on Tuesday, 15 June 2021.