Supporting microbiome-based projects
Smaltis harnesses the power of microbiota for health and well-being purposes, with customized-in vitro services in microbiology and molecular biology.
Smaltis thus supports the various stages of development of products derived from a microbiota and/or modulating a microbiota, providing complete data on candidates and optimizing them.
Studied products
Prevention & Well-being for health benefits
Nutraceutical (Dietary supplements – Feed) & Cosmetic
> Probiotics, Prebiotics, Postbiotics, Synbiotics
Treatment of different pathologies/therapeutic areas
Pharmaceutical & Medical devices
> Pharmabiotics, LBP, Small molecules, Biologics
Securing regulatory framework filling
Smaltis gives support in the regulatory documentation about product quality, safety, and efficacy, according specific guidelines to apply.
Scientific studies’ design are adapted to fit with regulatory expectations – helping reduce risks in the development of products and earn time, by mastering the science and implications.
- Early Clinical Trials with Live Biotherapeutic Products: CMC Information - Guidance for Industry. FDA, Updated June 2016
- Entering First-in-Human Clinical Study With a Single-Strain Live Biotherapeutic Product: Input and Feedback Gained From the EMA and the FDA. Frontiers in Medicine, August 2021
- Live Biotherapeutic Products, A Road Map for Safety Assessment. Frontiers in Medicine, June 2020
- Guidance on the assessment of bacterial susceptibility to antimicrobials of human and veterinary importance,EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). EFSA Journal 2012
Our services
ADVANCED STRAIN CHARACTERIZATION
YOUR NEEDS
1. Screening of strain candidates and help in decision making
2. Safety assessment for supporting candidate selection and identification of required optimization
3. Bringing strategic scientific data for regulatory filling
OUR TECHNIQUES
Genotypic analysis
Phenotypic analysis
Growth kinetics
Cell interaction
EXAMPLES OF SERVICES
Antibiotic susceptibility profile, hemolytic activity, phages production, cytotoxicity, resistance to transit pathway, virulence profile…
Genotyping, presence of plasmids and mobile genetic elements, morphology, gram staining, electronic microscopy photography, transmission of antibiotic resistance, fitness and viability, motility, conditions culture, growth kinetics, acidification kinetics, growth at different temperatures and pH values, tolerance to NaCl, aerotolerance, bile salts hydrolytic activity, aggregates formation, catalase and oxidase profile, sporulation capacity, endotoxins production, proteases production, production of folate, acidification of the substrate, production of biogenic amines such as histamine and tyramine, mutagenesis ability (Ames test), virulence, adhesion ability (biofilm initiation), antagonist effect against other strains, cell adhesion and invasion, transepithelial electrical resistance (TEER).
STRAIN OPTIMIZATION – GENOME EDITING
YOUR NEEDS
1. Genomic bacteria modification for safety risk management & improvement of strains
2. Recombinant product development to strengthen therapeutic efficacy or to add specific functionalities linked to molecule expression
OUR TECHNIQUES
Gene deletion
Gene replacement
Gene insertion
Mutagenesis
Cloning
EXAMPLES OF SERVICES
Deletion of virulence genes, phages-encoding sequences, gene insertion and gene expression optimization for therapeutic molecules production…
Deletion of factors linked to strain diffusion, mitigation of transmission of antibiotic resistance and pathogenicity, attenuation of virulence factors, elimination of plasmids, modification of sporulation phenotype…
Description of genetic modification, assessment of modification stability.
MECHANISM OF ACTION
YOUR NEEDS
1. Screening of candidates based on MoA, health-related properties & metabolic pathways
2. Development of tools and models to document MoA for R&D support and regulatory compliance
3. Identification of biomarkers for efficacy assessment during (pre)clinical phases or future companion tests
OUR TECHNIQUES
Culture & Co-culture
Eukaryotic cell models
Metabolic pathway studies
Models development from various samples
EXAMPLES OF SERVICES
Metabolization of a compound involved in a pathology, study of the competition with a microorganism, assessment of cytokines production, analysis of impact on cell infection…
BIOMANUFACTURING EARLY PROCESS DEVELOPMENT
YOUR NEEDS
1. Optimization of bioprocess & culture conditions (R&D and small-scale)
2. Method Development for Analytical Quality Controls of strains cultured in fermenters or metabolites expressed
OUR TECHNIQUES
Strains behavior assessments within different culture conditions
Definition of key parameters and adapted methods for analytical controls
EXAMPLES OF SERVICES
Development of steps of manipulation and culturing before the initial cell bank, method development to analysis rate of therapeutic molecules expression…
IN VITRO MONITORING DURING (PRE)CLINICAL PHASES
YOUR NEEDS
1. Candidates impact assessment on animal or human samples, post-administration
2. Biomarkers monitoring for diagnostic research tests or specific study of the fate of a strain after application
OUR TECHNIQUES
Strains or biomarkers monitoring
Post metagenomic studies of human/animal microbiota from different clinical samples
EXAMPLES OF SERVICES
Clinical samples analysis to confirm mechanism of action or efficacy, identification of biomarkers of interest, data correlaton with patients clinical state…
Case studies
Impact of a therapeutic compound against a bacteria involved in Crohn disease, from preclinical to clinical phases
Implementation:
Preclinical phase / working on isolated strains
-Assessment of adhesion & invasion properties of strains isolated from patients, on an intestinal cell line, in the presence and absence of the compound
-Development of aggregation assays to visualize interaction between the compound and FimH protein
Phase I b clinical study / working on biopsies
-Tailor-made procedure to isolate and dissociate « adherent » bacteria from « invasive » bacteria from intestinal biopsies
-Confirmation of interaction between the compound and these « biomarker bacteria »
Phase II clinical study
-Continued work on the Phase II clinical trial
Global characterization of a strain used as a Live Biotherapeutic Product
Objective:
As part of the development of a LBP for use in cancer immunotherapies, provide characterization data of the strain.
Context:
Data for regulatory authorities, before initiating clinical studies.
Implementation:
• Adhesion/Invasion to intestinal cells
• Cytotoxicity
• Mutagenic potential
• Aggregates formation
• Sporulation ability
• Motility
• Resistance to bile salts
• Endotoxin production
