Adenoviral Reference Material Working Group
Bid Submission Form
Long-term Stability Studies
RFP 12.0
Item for Submission
An Ad5 Wild-type Virus is being produced as a reference material for use in defining particle number and infectious units of adenovirus gene therapy vectors. This RFP invites laboratories to participate in the characterization phase, specifically to perform analyses that help us understand the long-term stability of the Reference Material. The Working Group plans to select a single institution to perform the long-term stability study. Laboratories will submit proposals to perform the long-term stability study based on the requirements described. Testing should begin with Timepoint T=0, within 30 days of manufacture. Filtration and vialing of the purified Reference Material are anticipated to take place in late August to early September 2001. All proposals are due to the Williamsburg BioProcessing Foundation by Monday, July 30. Electronic submissions are preferred.
General Requirements for Bidding
An Adenovirus 5 WT reference material is being produced under the guidance of a Working Group. The producing institution will provide a provisional particle concentration as part of a Certificate of Analysis along with confirmation of identity, functionality, purity, and freedom from adventitious agents. Particle concentration and infectious titer will be assigned to the reference material through measurements made by different laboratories, all performing methods provided by the Working Group (see RFPs 8.0 and 9.0). The Working Group may also incorporate data gleaned from the performance of other methods into the assignment of particle concentration, including those data developed as part of the stability studies on the Reference Material.
The timepoint T=0 will be defined as the date of manufacture/filtration. Initial stability indicating tests should be performed within 30 days of the date of manufacture (early to mid September) and will be assumed to reflect the true T=0 timepoint. Testing for other time-points will be allowed a +/2week window.
A long term stability study should focus on the following:
- a commitment to monitor stability of the Reference Material when stored at - 55°C and at -20°C over a period of 5 years (2001 until 2006),
- a commitment to perform stability indicating tests that at a minimum include the following analytical methods:
particle number by the OD260nm/SDS method supplied by the Working Group (see RFP 8.0),
infectious titer by the method supplied by the Working Group (see RFP 9.0), and
analytical anion exchange HPLC, with the method supplied as part of the proposal [Reference: P.W. Shabram, D.D. Giroux, A.M. Goudreau, R.J. Gregory, M.T. Horn, B.G. Huyghe, X.D. Liu, M.H. Nunnally, B.J. Sugarman, and S. Sutjipto. Analytical anion-exchange HPLC of recombinant type-5 adenoviral particles. Human Gene Therapy 8, 453-465 (1997)]
- a commitment to test for sterility at selected time-points over the five-year period (the Working Group suggests T=0, T=6 months, T= 2 years, and T=5 years),
- a commitment to perform an appropriate number of replicates and sample time-points for the three key stability indicating methods over the five-year period (suggested time points are 0, 6, 12, 18, 24, 36, 48,and 60 months), and
- a willingness to report data back to the Working Group at regular intervals, with the expectation that all T=0 timepoint data will be reported as soon as possible after completing the analyses.
Other analytical methods/characterization may be proposed in addition to the three methods listed. The proposal should include detailed information on the proposed method, data supporting its intended use (or publications), and information regarding the laboratory personnel’s experience with the proposed method. Such additional methods might include: RP-HPLC analysis, particle size analysis, light scattering analysis, container integrity, etc. Refer to RFP 10.0 for additional suggestions.
Each laboratory submitting a proposal for the long-term stability study RFP should provide a statement describing their experience and capacity to perform a long-term stability study. Methods should be described in as much detail as possible with specific attention to the proposed method of thaw, mixing, and storage. The statement should specifically address:
- the amount of Ad5 WT Reference Material that will be required to perform the proposed analyses (number of vials),
- a complete description of the laboratory’s anion exchange analytical HPLC method, preferably in the form of an operating procedure including a description of the assay reference standard and stability,
- the laboratory’s experience in performing the 3 required procedures (OD 260nm/SDS, infectious titer, analytical anion exchange HPLC),
- the qualifications of the personnel involved in performing the procedures and reviewing the data,
- the equipment that will be used and its calibration status,
- the specific strategies or protocol outlines for the stability study, including timing of samples and numbers of replicates per time-point, so as to address:
- stability at -55°C over the five-year period,
- stability at -20°C over the five-year period, and
- container integrity over the five-year period
- the laboratory’s plan for submitting stability data to the Working Group, and
- the laboratory’s readiness to begin testing in early to mid September 2001, with analyses completed within 30 days of T=0.
For laboratories wishing to also submit a proposal to perform additional methods of monitoring stability in addition to three required methods, the proposal should include:
- the amount of Ad5 WT Reference Material that will be required to perform the proposed analyses (number of vials),
- a complete description of the method, preferably in the form of an operating procedure,
- data supporting the intended use of the method (historical data, publications, etc.),
- the laboratory’s experience in performing the proposed procedure,
- the qualifications of the personnel involved in performing the procedure and reviewing the data,
- the equipment that will be used and its calibration status,
- the laboratory’s plan for submitting stability data using this method to the Working Group, and
- the laboratory’s readiness to begin testing in late early to mid September 2001, with analyses completed within 30 days of T=0.
Documentation Requirements
Capability statement with regard to performing the spectrophotometric procedure addressing the points listed above.
Submission and Deadline
Submit the completed form and all requested information for receipt by Monday, July 30, 2001 to the address below. Electronic submissions are encouraged. Final decisions will be communicated by or about August 31, 2001 at the latest. Testing is anticipated to begin in mid to late September. Please note that all information submitted will be publicly available. Please do not mark any information confidential, as we cannot honor that request. Please include an estimated cost and market value of all goods and services donated. Participants will be responsible for the cost of shipping the Reference Material to their location (express courier, dry ice). The estimated cost for US domestic locations is US$65 - $100, but is dependent on the amount of reference material to be shipped.
Williamsburg BioProcessing Foundation
Attn: Adenovirus Reference Material Working Group
P.O. Box 1229
Virginia Beach, VA 23451
PH:757-423-8823
FAX:757-423-2065
EMAIL:
Bid Submission Form
Long-term Stability Studies
RFP 12.0
Please complete the following fields:
Contact Information – RFP 12.0
*Contact Individual:Institution:
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*If laboratories are submitting a proposal as a group, a main contact should be provided along with contact information for each participating laboratory (attach additional copies of this form).
Please indicate if your institution is also submitting proposals for the other activities:
Determination of Particle Concentration
Determination of Infectious Titer
Short-term Stability Study
Other Characterization
Donation of Supplies/Other Services for Characterization Phase
Long-term Stability Form, RFP 12.0June 29, 2001Page 1 of 4