CfP-2 Vaccine platform technologies

Chemistry, Manufacturing, and Controls (CMC) template
Instructions for applicants:
To support your Step 2 application for CEPI’s CfP-2 on vaccine platform technologies, this template requests the current and predicted CMC process and yields. We recognize that your programs may be only in pre-clinical development at this time, however, projecting the process for later development stages, based on experience with other programs, helps to understand the strategic approach and projected outcomes, should early clinical stages be successful. We realize that your specific process may have gaps in some items in the following tables and that some aspects may be considered as works in progress, or not applicable to your particular technology, in such case, please input N/A. However, we ask you to complete the table to the best of your ability and leverage existing experience when it is available.
NOTE: Where applicable, please state any assumptions or other reference processes used to populate this template. For non-traditional production processes, please specify units of measure in the comments column.
The text format requirements for all Step 2 documents are:
-  Calibri light theme font size 10
-  Single spacing

Process specifications:

Parameter / Development stage / Comments (specify if yields are achieved or projected)
Pre-clinical / Clinical P1/P2 / P3/Stockpile/ Commercial
Anticipated clinical dose (units/dose: mcg, PFU, etc.) and Anticipated dose volume
Cell line
Scale of USP
Yield of USP (d/L)
Harvest process
DSP step 1 (% recov.)
DSP step 2 (% recov.)
DSP step 3 (% recov.)
DSP step 4 (% recov.)
DSP step 5 (% recov.)
DSP step 6 (% recov.)
DSP step 7 (% recov.)
DSP step 8 (% recov.)
DSP step 9 (% recov.)
DSP step 10 (% recov.) and estimated overall yield
DS storage temp
DP storage temp
Existing data on storage stability of in- process fractions?
DSP recovery (%)
DS productivity (d/L)
Formulation/fill/finish (stabilizers, adjuvants, final container, delivery device, lyophilized, etc.)
Proposed presentation (single dose vial, multi dose vial, Prefilled syringe, etc.) and volumes.
Estimated Cost of Goods
Please state CMOs, (if any and stage of contract negotiations (Existing Contract, MOU, Preferred supplier status, etc.)
Key source materials
Animal derived raw materials
Single use components
GMP-certified ingredients confirmed (Y/N)
Are there components that could result in difficulties of acceptance in Muslim countries (material from pork or canine origin)?
Additional Information
·  Please indicate sources of key specialty raw material/device to be used in the process.
·  Do you have FTO? Please indicate any existing CMC-related IP and its potential impact on freedom to operate.
·  Please indicate your knowledge of other products on the market or in clinical testing using the same or similar technology.
·  Have you had any preliminary discussions with any competent regulatory authority regarding any aspect of the process?
·  If using an adjuvant other than Aluminium salt, describe previous clinical or commercial experience.

i.  Confirm status of the following for each target in the application and other targets if applicable:

Item / Y/N/NA / Quantity / Mfg. by: / Comment
MCB prepared
MCB released
WCB prepared
WCB released
MVS prepared
MVS released
WVS prepared
WVS released
Pre-clinical batches prepared
Clinical batches prepared
Additional Information
·  For RNA/DNA platforms consider MCB/MVS equivalent to library or template generation, USP equivalent to any amplification step and DSP equivalent to the removal of in-process impurities.

Formulation Stability Data:

Please confirm the following for each target:

Stage: (state stability where available) / Time at 5oC
(mo.) / Time at 25 oC (mo.) / Time at elev. temp (mo.) / Time at frozen temp (T, mo.) / Prescribed Storage (Temp/time) / Comments
MCB stability studies
MVS stability studies
DS stability studies
DP stability studies
Stability of any specialty process ingredient

List Release Assays (current and projected, “in-sourced and outsourced”):

Stage / MCB / MVS / DS / DP
Purity (residuals for DS and DP)
Potency
Sterility
Safety
Stability
Key Characterization Assays
Identity
Additional Information
·  For potency assay and key characterization assays, please provide information of the status of the assay development – performed under non-GMP, assay qualified, assay validated, performed under complete GLP, etc.
·  For RNA/DNA platforms –Please elaborate your strategy to test integrity of NA sequence, and how RNAse/DNAse activity is managed.

Summary of Platform Experience to date:

Please list all experience, including experiences of others using the same platform/process:

Parameter / Disease Target / Disease Target / Disease Target / Disease Target
Target Molecule
Pre-clinical Scale
Process yield at DP (d/L)
P1/2 Clin. Scale (L)
Process Yield at DP (d/L)
Timing – sequence to FIH (weeks)
P3 Clin. Scale (L)
Process Yield at DP (d/L)
Proposed Commercial Scale (L)
Process Yield at DP (d/L)


Anticipated detailed timing for delivering FIH clinical materials (include DS, DP, Adjuvant, devices, etc., as appropriate):

Time (weeks) / Tasks started / Tasks completed
0 / Received Sequence of pathogen target antigen / Received Sequence of pathogen target antigen
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2
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16
Additional Information
·  If the current process does not meet CEPI’s aspirational timeline of 16 weeks from identified antigen to product release, please indicate your strategy (if any) to speed up the process.
·  Specify timing of toxicology studies, current and proposed.

Anticipated detailed timing for completing 100,000 dose supply quantity of released DP from production order (include DS, DP, Adjuvant, devices, release testing, etc., as appropriate):

Time (weeks) / Tasks started / Tasks completed
0 / PO for 100,000 doses received / PO for 100,000 doses received
1
2
3
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5
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8
Additional Information
·  Where using single use systems – please specify the inventory management strategy for rapid response (100K, 1M dose PO’s)
·  If the current process does not meet CEPI’s aspirational timeline of 8 weeks to produce 100,000 doses, please indicate your strategy (if any) to achieve such a goal.

Anticipated use of delivery device (as applicable)

Delivery Device/System information
·  Describe the delivery device supply chain have you established
·  Is the same delivery device intended for use, both in clinical trials and in the developing world setting?
·  If yes, what is the capability for large scale manufacturing needed to match the 100,000 dose stock pile scale?
·  If not, what are the required steps to finalize a suitable delivery system? Would there be a need for bridging studies? What are the risks related to the device development and manufacturing? What are the regulatory pathway for such a combination product (drug device combination)?
·  What is your status when it comes to implementation of the new MDR and ISO13485-2016?
·  Do you have a system to prevent re-use of disposables (if applicable)?
·  What is the key evidence supporting the selected delivery method, dose (volume), electroporation parameters and human tolerability data you intend to use in the current project
·  Provide an indicative timeline of device availability to cover 100,000 doses
·  Provide a detailed planning for the deployment of the device to support/guarantee the proposed First in Human Study timelines in this document
Time (weeks) / Tasks started / Tasks completed
0 / Received Sequence of pathogen target antigen / Received Sequence of pathogen target antigen
1
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3
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CfP -2 CMC Specification Template