COMMERCE BUSINESS DAILY ISSUE OF AUGUST 10,2000 PSA#2661 National Cancer Institute, Research Contracts Branch, PSAS, 6120
Executive Blvd, EPS/Room 638, Bethesda, MD 20892-7227 99 -- PURIFY MONOCLONAL ANTIBODY-35 (MAB-35) AND CONJUGATE MAB35-RICIN
SOL NCI-RFQ-00145-NV DUE 082400 POC Deborah Moore, Purchasing Agent and
Todd Cole, Contracting Officer (301) 402-4509 This is a combined
synopsis/solicitation for commercial services, prepared in accordance
with the format in FAR 12.6, as supplemented with additional
information included in this notice. This announcement constitutes the
only solicitation and a separate solicitation will not be issued. This
solicitation, No. RFQ-NCI-00145-NV includes applicable provisions and
clauses in effect through FAR FAC 97-19. The acquisition is being made
in accordance with the test program for using simplified procedures
for certain commercial items authorized in FAR 13.5. The solicitation
is set-aside for small business. The Standard Industrial Classification
Code is 2836, and the business size standard is 500 employees.
BACKGROUND: The National Cancer Institute (NCI), on behalf of the
National Institute for Neurological Disorders and Stroke, requires
monoclonal antibody-35. This project involves the production and
delivery of an immunotoxin for clinical trials for the treatment of a
variety of muscle spasm disorders. In animal models, use of an
immunotoxin specific for the muscle acetlycholine receptor is effective
in reducing muscle strength (see Neurology Hott, JS, Dalakas, MC, Sung,
C, Hallett, M and Youle RJ: A skeletal muscle-specific immunotoxin for
the treatment of focal muscle spasm. Neurology 50: 485-491, 1998).
REQUIREMENTS: Independently, and not as an agent of the Government, the
Contractor shall perform the commercial services described below and
provide all personnel, material, equipment, and facilities not
otherwise specified and provided by the Government. Specifically, the
Contractor shall, under Good Manufacturing Practices (cGMP), purify
monoclonal antibody-35, (Mab-35) purified bulk and conjugate Mab-35 to
Ricin supplied by NIH, purify the conjugate and make available bulk
container products for phase III clinical trials. Following reviews of
validation and qualification documents for facility, systems,
equipment, raw materials, and process used in this project, working
banks of purified monoclonal antibody -35, and purified Mab-35
conjugate to Ricin shall be prepared and qualified and stored on-site
at the Contractor's facilities. Mab-35 purification and conjugation to
Ricin shall be performed at an FDA-approved clinical manufacturing
site. Two production lots of the Mab-35 / Ricin shall be produced under
cGMP guidelines as the primary final bulk product and a backup bulk
lot. If the backup lot is not needed for production of final container
product, then the backup lot shall serve as a control lot for QC
testing and archives and as a validation lot. Mab-35 shall be purified
from mouse ascites, supplied to contractor, by ammonium sulfate
precipitation and DEAE Sepharose chromatography. Conjugation of Mab- 35
to Ricin shall be performed by adding DTT in phosphate-buffered saline
to antibody, and incubating for 30 minutes. This antibody-DTT mixture
will be applied to a G-25, gel filtration column equilibrated with
PBS. Peak antibody fractions will be collected and pooled. Then, Ricin
will be mixed with DMF containing the bi-functional cross-linking
agent, MBS and incubated at room temperature for 30 minutes. The
Ricin-MBS will be immediately reacted with fresh reduced antibody and
incubated at 4 degrees overnight. The conjugate will then be separated
from unreacted ricin by HPLC on a TSK 3000 SW column in sodium
phosphate buffer (pH 7.2), or another size exclusion column. The peak
fractions from several runs containing both unreacted antibody and ITX
(immunotoxin) will be pooled and loaded onto an immobilized
D-galactose affinity column at 4 degrees. After the column is flushed
with PBS to remove unreacted antibody, lactose will be run over the
column to elute the purified ITX. Each GMP lot shall contain at least
100mg. of purified Mab-35-ricin ITX. The final bulk products shall
undergo analytical and safety testing by the Contractor's quality
control group and the SNB of NINDS at the National Institutes of
Health, prior to release for formulation and final container filling.
Review and approval of batch records and test results shall be
performed by the Contractor's Quality Assurance (QA) group. The final
bulk and container products shall be stored at 4 degrees in secure
refrigerators at the Contractor's location. The final container
products shall be subjected to safety and analytical testing conducted
by the Contractor's Quality Control group and the SNB of NINDS at the
National Institutes of Health. Quality Assurance by the Contractor
shall encompass reviewing of batch records, final container test
results, and final manufacturing reports. Upon approval, the Contractor
shall issue certificates of analysis and release the final container
products. Final manufacturing reports shall be provided to the NINDS or
designated entity as noted by the Project Officer. The final bulk and
final container products shall be enrolled into a stability testing
program for the Mab35-ricin conjugate ( ITX) . Upon written
notification from the Project Officer, the Contractor shall ship at 4
degrees, the final container products to theSNB/NINDS repository in
Bethesda, Maryland. The Contractor shall adhere to the following
objectives and timelines in completing the above work: MONTH 1 --
1.Review validation and qualifications of off-site manufacturing plant;
2. Implement technology transfer process of off- site manufacturing
Facilities; 3. Review SOPs and prepare batch records for GMP
purification of Mab35 & Mab35-ricin conjugate; 4. Begin purification of
Mab35 ascites as a working bank from ascites provided to contractor.
MONTH 2 Complete purification of Mab35 ascites by ammonium sulfate
precipitation and DEAE Sepharose Chromatography, in manufacturing
cleanroom by following processing scheme below : a.mix ascites with an
equal volume of cold saturated ammonium sulfate, and stir at 4 degrees
for 20minutes; b.centrifuge ascites mix in Sorvall 34 rotor at 8000 rpm
for 10min., remove supernate and save at 4 degrees C. (Fraction S); c.
resuspend ascites pellet (Fraction P) in 20mM Tris (buffer A), pH 7.9;
d. dialyze Fraction P against 2 changes of 2L of 20mM Tris buffer, pH
7.9 containing 40mM NaCl (Tris buffer D), at 25 C over a 4hr. period or
against Tris Buffer A . Repeat dialysis with fresh 2L buffer overnight;
e. Remove sample from dialysis bag & place in clean glass centrifuge
tubes; f. Centrifuge in Sorvall 34 rotor at 8000 rpm for 10 min. to
remove any aggregated protein. (save 25 ul for SDS gel); g. Apply
fraction P over pre-poured & packed DEAE-sepharose column and elute
with a sodium chloride gradient, (buffer B & buffer C) low & high salt.
Collect fractions from column gradient in tubes of 2ml on fraction
collector. (buffer B= 20mM Tris+20mM NaCl) & (buffer C=20mMTris + 400mM
NaCl); h. Read fraction tubes on spectrophotometer at A280 and store
tubes at 4 degrees until needed; 2. Analyze Mab35 fractions collected
by Quality Control methods at the Contractors; and at SNB, NINDS of the
National Institutes of Health using the following: a. Perform SDS-PAGE
protein analysis on fraction A, (pre-dialyzed ascites)Fraction P, (
dialyzed Mab35 pre column), a MW standard and fractions of interest
from column gradient samples; b. PAGE should be run using Tris- Glycine
1x buffer; c. Gel should be stained with Coomassie Blue Reagent and
destained with 10% acetic acid; d. Using A280 results and gel samples
as a guide, pool fractions with highly purified IgG and dialyze and/or
concentrate; e. Dialyze against 2L PBS ph 7.4 and change PBS buffer 1x
over a 2-4 hr. period / or overnight to remove sucrose; f. Remove
sample from bag as carefully as possible and place in clean tube; g.
Centrifuge in clean tubes in Sorvall rotor for 10min at 8000 rpm; h.
Pour supernate into clean sterile tubes and calculate concentration of
Mab35 antibody. MONTH 3 -- 1. Perform conjugation of Mab35 antibody to
ricin by following methods: a. Add DTT in phosphate-buffered saline
(PBS) to 10-50mg of antibody, and incubate for 30 min to partially
reduce the antibody; b. Apply this antibody-DTT mix to a G-25, gel
filtration column equilibrated with PBS, collect fractions and pool
peak antibody fractions; c. Mix ricin, supplied by NIH, 20-100mg in PBS
with DMF containing the bi-functional cross-linking agent, MBS
(m-maleimidobenzoyl-N-hydroxysuccinimidyl) ester; d. Incubate mixture
at room temperature for 30 min. Ricin-MBS is then immediately reacted
with freshly reduced antibody and incubated at 4 overnight; e. The
conjugate is then separated from unreacted ricin by HPLC on a TSK 3000
SW column in 0.1M sodium phosphate buffer (pH 7.4), or another size
exclusion separation method; f. The peak fractions from several runs
containing both unreacted antibody and ITX (immunotoxin) shall be
pooled and loaded onto an immobilized D-galactose affinity column.
(Pierce) at 4 degrees Celsius; g. The column is then flushed with PBS
to remove unreacted antibody, and 0.1M lactose is run over the column
to elute the purified ITX. MONTH 4 -- 1. Review of QA batch records and
testing and release of final bulk product; 2 . Formulate final bulk
product in Sterile PBS and Human Serum Albumin at 1mg/ml as before in
bulk container in cleanroom; 5. Transfer bulk containers of Mab-35 and
Mab-35 Ricin on 4 degrees celcius to NINDS; 6. Complete archival
storage of final container product at 4 degrees celsiuis in a secure
refrigerator for stability testing; 7. Perform quality control safety
testing of final container product including: a. microbial sterility
testing, b. Mycoplasma and spiroplasma testing, and c. Endotoxin
testing; 8. Perform QC analytical testing of final container product
including: a. Purity-SDS- PAGE analysis with scanning densitometry and
EM, b. Identity -- Western blot analysis, c. Strength-BCA protein
quantitation assay; 9. Perform QA auditing of batch records and final
manufacturing report, release of final container product, and issuance
of certificate of analysis; 10. Prepare and submit final manufacturing
report by project manager to sponsor; 11. Perform stability testing of
final bulk and container product per existing stability program; and
12. Finally, in addition to the above, documentation of the production
procedure and the specifications of the final material, along with
certificates of the GMP techniques used throughout the process and
bottling, shall be provided in sufficient detail to allow for the FDA
review and approval. Shipping and Delivery: Mab35 and Mab35-ricin
conjugate final container products shall be packaged according to the
requirements herein. The products shall be shipped at 4 degrees to a
location within Bethesda, Maryland area. The exact location shall be
documented within the anticipated award document. All products shall be
shipped at the same time. Furthermore, the products shall be shipped
F.O.B. destination or F.O.B. origin with transportation insurance
provided by the vendor with inside delivery to the location specified
within the anticipated order. It is planned that final delivery of the
product and all documentation will be prior to June 1, 2001. PRICING:
Quotations must include a complete fixed price which includes the
product, all certifications, warranties, reports, other fees/costs,
shipping, and insurance, if F.O.B. origin. EVALUATION CRITERIA: The
technical portion of quotations will be reviewed by a panel of at least
three NIH experts. The technical portion of quotations will receive
paramount consideration in selecting a vendor. However, cost/price will
also be a determining factor in the event that two or more offers are
determined to be essentially equal following the evaluation of
technical factors. Vendors submitting quotations shall also provide
three references of organizations that have produced similar monclonal
antibodies within the past three years. The references may be used in
the event that two or more offerors are considered essentially equal
after the technical and price evaluations. In any event, the Government
reserves the right to make award to the vendor whose offer provides the
greatest overall value to the Government. The major evaluation factors
for this RFQ include technical and price factors. MANDATORY
QUALIFICATION CRITERIA: The following is a mandatory qualification
criterion that establishes conditions that must be met in order for
your quote to be considered for award: vendor/quoters must demonstrate
that they own or have legal access to an FDA-approved clinical
manufacturing site to perform the requirement herein. TECHNICAL
EVALUATION CRITERIA: The following technical evaluation criteria will
be used by the Government when reviewing the technical portion of the
quotation. The criteria below are listed in the order of relative
importance with weights assigned for evaluation purposes: 1. Technical
understanding of the requirements to produce two production lots of
Mab-35/Ricin under cGMP guidelines relative to technical approach,
techniques, and quality assurance and control to ensure the required
purity. (45%); 2. Evidence of having produced similar monoclonal
antibodies under cGMP guidelines. In addition, availability and
suitability of personnel to perform such monoclonal antibody production
relative to training and experience. (40%); and 3. Suitability of
facilities and equipment for production of Mab- 35/Ricin under cGMP
guidelines (15%). Total weighting of above factors is equal to 100%.
Quotes must be submitted on an SF-18 or SF-1449. Quotes must be
accompanied by a completed "Offeror Representations and Certifications-
Commercial Items -- with Duns Number Addendum," signed by an authorized
representative of the vendor. Quoters must submit an original technical
proposal/quotation plus descriptive literature, warranties, and/or
other materials that demonstrate that their offer meets all of the
foregoing requirements. The technical proposal's documentation shall
also include curriculum vitae for the contractor staff that will be
involved in the production; legal proof of ownership or access to a GMP
facility for producing the above material; and a narrative of
experience in producing similar products via similar commercial
processes. In addition, four (4) copies of the technical proposaland
all materials shall be submitted with the original. This solicitation
incorporates the provisions at FAR 52.212-1, INSTRUCTION TO OFFERORS --
COMMERCIAL ITEMS -- DEVIATION FOR SIMPLIFIED ACQUISITIONS; FAR
52.212-3, OFFEROR REPRESENTATIONS AND CERTIFICATIONS -- COMMERCIAL
ITEMS, along with the DUNS NUMBER ADDENDUM; and The resulting contract
will incorporate the requirements contained in paragraphs (a)and (d)
of the clause at FAR CLAUSE 52.212-4 CONTRACTS TERMS AND CONDITIONS
COMMERCIAL ITEMS and FAR Clause 52.212-5, CONTRACT TERMS AND CONDITIONS
REQUIRED TO IMPLEMENT STATUTES OR EXECUTIVE ORDERS- COMMERCIAL ITEMS-
DEVIATION FOR SIMPLIFIED ACQUISITION. The contract will also
incorporate the following FAR clauses cited in paragraphs (b) and (c)
of the latter clause: FAR 52-222-26, EQUAL OPPORTUNITY; FAR 52-222-35,
AFFIRMATIVE ACTION FOR DISABLED VETERANS AND VETERANS OF THE VIETNAM
ERA; FAR 52-222-36, AFFIRMATIVE ACTION FOR WORKERS WITH DISABILITIES;
FAR 52-222-37; EMPLOYMENT REPORTS ON DISABLEDVETERANS AND VETERANS OF
THE VIETNAM ERA; and FAR 52.232-34, PAYMENT BY ELECTRONIC FUNDS
TRANSFER OTHER THAN CENTRAL CONTRACTOR REGISTRATION. Interested vendors
may contact Debbie Moore, Purchasing Agent, at (301)-402-4509 (Fax:
(301)-402-4513) to receive full text copies of the representations and
certifications or other cited provisions and clauses. Offerors may
submit proposals that depart from stated requirements. Such proposals
shall clearly identify why the acceptance of the proposal would be
advantageous to the Government. Any deviations from the terms and
conditions of the solicitation, as well as the comparative advantage to
the Government, shall be clearly identified and explicitly defined. The
Government reserves the right to amend the solicitation to allow all
offerors an opportunity to submit revised proposals based on the
revised requirements, if it deems it appropriate. Any questions
pertaining to this solicitation and requirement shall be submitted by
August 15, 2000. Complete quotations and all related materials must be
received in this office no later than 2:00 pm EDT on August 24, 2000.
Please cite the solicitation number, RFQ-NCI-00145-NV, on your
quotations, including all copies of the technical portion of quotation.
Posted 08/08/00 (W-SN483750). (0221) Loren Data Corp. http://www.ld.com (SYN# 0323 20000810\99-0008.SOL)
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