Safety Assessment (Toxicology Services)

IND Enabling Studies

NDA Enabling Studies

Impurity

Pathology Services

Immunohistochemistry

• Immunohistochemistry (IHC) combines anatomical, immunological and biochemical techniques to identify discrete tissue components by the interaction of target antigens with specific antibodies tagged with a visible label.
• IHC makes it possible to visualize the distribution and localization of specific cellular components within cells and in the proper tissue context

BrdU- IP route 50 mg/kg Intestine 10x

BrdU- IP route 50 mg/kg Intestine 20x

EpiSkin® Test in vitro Skin Corrosion & Irritation

What exactly is SEND?

• SEND (Standard for Exchange of Nonclinical Data) is a new electronic formatting requirement for research data submitted to the US FDA in certain Investigational New Drug (IND), New Drug Application (NDA), Abbreviated NDA Application (ANDA), and Biologic License Applications (BLA).
• Study Data Tabulation Model (SDTM), the electronic standard used for clinical regulatory submissions to the FDA, is now required for nonclinical research.
• CDISC (Clinical Data Interchange Standards Consortium), a non-profit standards development organisation comprised of representatives from pharma, biotech, CROs, vendors, consultants, and the FDA, produced SEND, SDTM, and related standards.
• FDA issued a final advice on the use of standardised electronic formats (such as SEND and SDTM) for applicable nonclinical and clinical submissions on December 17, 2014. Since December 2016, these electronic standards have been required for all investigations.

SEND’s Importance:

• The FDA use SEND to examine data in study applications.
• Rapid access to vast amounts of data, resulting in a quicker FDA review and, as a result, a shorter time to market.
• Uses controlled terminologies.
• Standardized formats.
• Enhanced data review.
• Eliminates data entry by agency.
• Enables data warehousing, analysis and visualization.
• Noncompliance can result in a refusal to file from the FDA and submission delays.

FDA’s SEND Implementation Timeline for All Sponsors, CROs, and Others

The final FDA guidance on standardised electronic formats, which was released on December 17, 2014, is now enforceable (i.e., SEND and SDTM will be required) as follows:

• For applicable NDAs, ANDAs, and BLAs: Studies starting after December 17, 2016
• For applicable INDs: Studies starting after December 17, 2017SEND 

SEND Readiness at Mavens

• Mavens started its evaluation in 2012
• The first SEND dataset for an in-house study was generated in June 2013
• Since then all FDA submission NDA studies performed at Mavens use SEND
• SEND data submission for 3 Carcinogenicity studies is on-going

Process of using SEND at Mavens

Study Director
⇓
Processing data in SEND format
⇓
Study team/QAU verifies all the modules, data
⇓
Ready for Submission

Mavens Ensures that data sets are 

• compatible with Study Reports.
• Without receiving a Refusal to File (RTF) from the FDA, the data is validated and loadable into the Nonclinical Information Management System (NIMS).
• Scientists reviewed the data to ensure accurate interpretation and prompt responses to any issues.

Dose confirmation studies (which are required by regulations) for animal toxicology, ecotoxicology, and genetic toxicology research are among Mavens’ capabilities.

• Analytical method development and validation for analysis of test item concentration in
  • Gavage suspensions / solutions
  • Dietary admixtures
  • In vitro incubations
  • Air inhalation samples
  • Reconstituted/aquarium water
  • Algal medium, etc.
• Testing stability and homogeneity of the test item in dose formulations

Bioanalytical support:

Mavens Bioanalytical Group specialises in the creation, validation, and analysis of quantitative LC-MS/MS methods. Compounds in discovery, preclinical (toxicology), and clinical development all benefit from bioanalytical services. For discovery research, tailor-made bioanalytical procedures are created. For investigations undertaken for regulatory submission, GLP-compliant bioanalysis is carried out utilising completely validated methodologies developed.

Bioanalysis of Small Molecules:

• Bioanalytical services to support FDA, EMEA, MHRA, and other global regulatory filings, as well as other research requiring analytical support.
• Excellent capacity to develop and verify bioanalytical procedures using cutting-edge LC-MS/MS and HPLC technology, with sensitivity reaching picogram levels.
• Developing non-GLP bioanalysis procedures that are fit for purpose.
• Precipitation, liquid-liquid extractions, and solid-phase extractions are all used to process samples.
• Capability for derivatization techniques, including method development and validation (e.g. for poorly ionizable chemicals).
• Analyte / metabolite(s) quantification in biological matrices such as plasma, serum, and blood samples in accordance.

Bioanalysis of Large Molecules:

• Ability to develop and validate methods in accordance with GLP guidelines.
• Method transfer employing ELISA methods, as well as feasibility, development, and   validation of bioanalytical methods.
• Commercially available ELISA kits were used for validation.
• ELISA-based peptide and protein bioanalysis capability
• In the preclinical stage (non-GLP and GLP studies).
• Neutralizing antibody assays, as well as immunogenicity/antigen-antibody assays.
• Biomarker assays capability.
• Identification and measurement of biomarkers

Mavens has a proven track record of executing GLP-compliant toxicity investigations for regulatory submission. Since 1992, when it became the first laboratory in India to receive GLP accreditation from the German Ministry of Health, Mavens facilities have been GLP recognised by the BfR German Health Ministry. W&V Netherlands accredits this facility in 1999, and Indian GLP authorities accredit it in 2005. Since 2001, the facility has also been AAALAC International certified. The facility was also India’s first GLP facility, having been inspected by the US Food and Drug Administration in 2012.

We’ve completed over 25,000 regulatory studies for submission to regulatory agencies throughout the world, including the USFDA, EMA, MHRA, TGA, Health Canada, and DCGI. Mavens can conduct all types of safety assessments (toxicology) required by agrochemicals, chemicals (REACH), dyes, and other similar products.

The toxicology team at Mavens takes pride in having 35 highly experienced study directors with an average of 15 years of industry and regulatory experience. Mavens also employs 9 toxicologists who are Diplomates of the American Board of Toxicology (DABT).

Safety Assessment studies are carried out in accordance with OECD GLP and study criteria established by international regulatory organisations such as the USFDA, USEPA (OPPTS), OECD, EEC, JMAFF, WHO, DCGI, DBT, and CIB of India, among others.

Our extensive range of GLP and non-GLP service offerings, together with our more than three decades of experience, ensure that we fulfil the current global toxicological testing criteria. Mavens’ skilled team ensures that studies are completed in the quickest time feasible, allowing regulatory submissions to be expedited.

The Institutional Animal Ethics Committee (IAEC), which is comparable to AAALAC International’s IACUC, reviews and approves all animal experimental protocols.

Mavens vivarium is one of the largest in South Asia, with over 80 rooms that satisfy international maintenance and operation requirements and is authorised by the CPCSEA, Government of India, and AAALAC International.

Mavens has developed more than 80 comprehensive IND packages for regulatory submissions around the world. In addition, the company conducts chronic toxicity, reproductive toxicity, juvenile toxicity, and carcinogenicity research on a regular basis. Until now, the company has completed 65 carcinogenicity studies (containing both pharmaceutical and agrochemical substances), the majority of which were for submissions to US and EU regulators. The company has a large historical control dataset in rats (Wistar and Sprague Dawley) and mice (Wistar and Sprague Dawley) (Swiss Albino).

In addition to conventional carcinogenicity studies, the company has completed a 6-month carcinogenicity study in the Tg RasH2 transgenic mouse model, which is a service offered by only a few global nonclinical contract research organisations.

The toxicology team at Mavens takes pride in having 35 highly experienced study directors with an average of 15 years of industry and regulatory experience. Mavens also employs 9 toxicologists who are Diplomates of the American Board of Toxicology (DABT).