RCGM And CDSCO Recommends Fast Track Processing Of Recombinant Vaccines Applications For COVID-19
All over the world, scientists are working around the clock to find a vaccine against COVID-19. Global experts estimate that a fast-tracked vaccine can bring a vaccine to market in approximately 12-18 months – if the vaccine development process goes smoothly from conception to market availability.
The Central Drugs Standard Control Organisation (CDSCO) and Review Committee on Genetic Manipulation (RCGM) recommends the rapid processing of recombinant vaccine development during COVID-19 pandemic under Rapid response Regulatory Framework. All the applications will be screened depending on the proper data and population.
Key Highlights of the Guidance Note
- Checklist of the conduct of pre-clinical toxicity (PCT) studies for recombinant vaccine development for COVID-19.
- Consideration of the evidence of preclinical data outside India and analysis of the quality of data regarding the vaccine
- Parallel application for clinical trial and PCT studies to CDSCO and RCGM, respectively.
- Consideration of data on clinical studies generated outside India and abbreviated pathway for vaccine based on scientific rationale and level of completeness of data in human trials.
The Vaccine production platform (live viral vector, DNA, Yeast/ cell line expression, etc.) and the anticipated end product (DS) substantiated with published literature regarding its quality attributes, safety and immunogenicity. Substantiation can be with unpublished literature as well (in-house research, patent needs, etc.). In such cases there should be substantial documentation like manuscripts, inhouse documents, etc.
|A1||The application to contain Table of contents, all pages serially numbered, and all cited annexure(s) included in the final application.||Required|
|A2||Approval(s) accorded so far for the product under development by IBSC, RCGM, IAEC, etc. approved by CPCSEA, etc. (approvals as per proforma and guidelines may be provided later when covid-19 pandemic improves.||Firm should apply for the appropriate approvals. Rolling submission allowed.|
|A3||Describe source of material (isolate, lab, country)||Required|
|B1||Describe origin of gene(s) coding the molecule under consideration (isolate, lab, organization country)||Required|
|B2||Provide Nucleotide and translated protein sequences||Required|
|B3||Information about the vector (Include restriction map, Promoter and Terminator used for the expression of recombinant gene, method of transformation, selection agent used, etc.)||Required|
|B4||Description of host organism characteristics/ Cell type to be Required used for expression and method of recombinant gene delivery||Required|
|C1||Intact mass analysis||Note: The data requirement vary depending on the type of vaccine. In case of DNA vaccine, sequence information of vector and target SARS CoV-2 virus, host cell DNA contamination etc. are important. Stability of the DP and its effective (efficacy) dose is a primary requirement for PCT studies.|
|Confirming the identity of the expressed gene product.|
|C2||Peptide mapping (overlay results of all batches) and N- [terminus amino acids sequencing data|
|C3||Secondary structure data by CD spectroscopy/Near and far UV visible spectra (overlay results of all batches)|
|C4||Fluorescence spectroscopy to provide evidence for similarity at high order structure (overlay results)|
|C5||Data on disulfide bond presence (when applicable)|
|C6||Charge heterogeneity (Data from Ion exchange chromatography, lsoelectrofocusing, etc. )|
|C7||Carbohydrate/glycan content analysis and details of components, as applicable|
|C8||Presence of aggregates (using any suitable method e.g. Size Exclusion Chromatography (SEC), Dynamic Light Scattering (DLS) etc.)|
|C9||Endotoxin/Pyrogen content (for each consistency batch)|
|C10||Host Cell Protein content (for each consistency batch)|
|C11||Host Cell DNA content (for each consistency batch)|
|D||Immune response/ Biological activity|
|D1||Specify Adjuvant and dose formulation. Specify laboratory. animal model used for assessing the immunogenicity (number, age, gender, strain), Vaccination protocol (site/dosage) concentration of antigen used, the immune response profile, antibody titers, etc. describe method of measuring antibody profile, antibody titres, etc. Provide data on antibody profile, antibody titre.||Required. This is critical for a vaccine candidate|
|D2||Assessment of neutralizing antibodies, if any. Describe method for assessment of neutralization antibodies, provided data on neutralization efficiency/specificity, etc.|
|D3||Report any adverse effect in animals||Required|
|D4||Polyclonal or monoclonal antibody product? If poly clonal, batch consistency data and if monoclonal, clone data and other sib clones availability|
|E||Formulation and Stability studies of Drug Substance (DS) and Drug Product (DP), proposed done|
|E1||Submit consolidated three batch data||Required for three batches|
|E2||SOS-PAGE analysis (preferably silver stained & in alignment with MW Marker) and confirming the identity by western blotting||Basic characterization for the Vaccine drug product. Detailed can be given with Tox. Report|
|E3||Overlay of Size Exclusion Chromatography analysis|
|E4||Data on bioactivity/bioassays|
|E5||Stability data on real time***, accelerated and stress studies of all batches of drug substance (DS) and drug product (DP) at defined time points for DS and depending on the proposed shelf life for DP |
***Up to one-month Real time stability data of DS and DP required at the time of Submission.
|Stability Program/ Protocol should be given in PCT application and with [the proof of start of stability for DS and DP. [The stability data can be submitted in rolling submission for special COVID 19 situations as stability of the compound is a primary requirement for PCT studies)|
|Storage temp. of DS and DP||Required|
|Stability studies results should be submitted along with C3b form.||With Toxicity report|
|Should include Real time, Accelerated stability and Stress stability for all data.||Plan should be for all three|
|E6||Define the composition of DP. Specify the adjuvant, excipients/stabilizers used in the formulation. In the case of multiple antigenic targets in the DP indicate the ratio of the 'different targets||Required|
|F||Acceptability criteria of the formulated material for preclinical safety studies(Acceptance limits should be set based on Indian pharmacopoeia for vaccines or equivalent regulation for general test parameters and in house criteria.)|
|F1||Specifications for DS and DP should be established around critical quality attributes.||Required|
|G||Proposed study plan for preclinical toxicity studies|
|G1||Whether the representative toxicology batch of DP is one of the RCGM approved consistency batch. If not, generate complete comparative data of this batch with that of the consistency batch approved earlier by RCGM.||Submit the batch size which should be sufficient enough to conduct characterization and PCT studies. Submit the profile of batch and COA after he batch is taken for PCT within a week of he testing is completed.|
|G2||List of preclinical toxicity and immunogenicity studies to be conducted. (including protocol/guidelines/standards to be followed)||Required|
|G3||Selection criteria for animals selected and numbers to be used in each group. Justification for the selection of animal model/numbers)||Required|
|G4||Submit detailed Pre-clinical toxicity & lmmunogenicity (sequence specific, non-specific to other proteins and with adjuvant, as applicable0) study protocols. Protocols should include route of administration, dosage to be tested (based on effective dose), basis of dose calculation, vehicle, mode of administration, volume of administration (single or multiple administration.||Required|
|G5||Provide address and accreditation status of the facility where studies are to be conducted.||Required|
|G6||Explain compliance of containment facility measures||Required|
|G7||Specify decontamination and disposal mechanisms.||Required|
|G8||Explain plans in case of any Emergency.||Required|
|G9||Attach copies of IBSC approvals of the Sponsor and CRO(s) (Photocopy of /BSC/ minutes wherein proposed studies were approved||Required (Online meetings are allowed).|
|H||Undertaking/ Declaration Letter Signatures To be signed in original by hand (Electronic/ scanned signatures not acceptable)||Required ( all legal signatures to be accepted)|
For SARS CoV-2 follow the Interim Guidance Document on Laboratory Biosafety to Handle COVID-19 Specimens available at IBKP portal.