Module 03: Data on API, Formulation and Requirement of Animal Studies

Approval of New Drugs in India

Before starting a clinical trial on new drug there is requirement of generation of lot of data on API (Active pharmaceutical ingredient), formulation and animal studies. This module covers the requirement of data on API, formulation and animal studies for new drug application.

1. Active Pharmaceutical Ingredient:

Source of bulk drugs /raw materials

a) In-house
b) Other than in-house

If source is other than in-house, a copy of consent letter from manufacturer of the bulk drug should be submitted and the manufacture of the bulk drug should also file application for the bulk drug. The applicant can either import or manufacture the API by themselves or they can obtain the same from some other indigenous source:
Import the API – Applicant has to file application along with all relevant documents and comply with further requirements for import of API.

Manufacture the API – Applicant has to also file application for API along with all relevant documents and comply with further requirements for manufacture of API.

Obtain the API from another manufacturer which is not yet approved by DCGI – In such case, the respective manufacturer of the API has to file an application separately in Form 44 along with treasury Challan of requisite amount with all relevant documents. Such application will be processed simultaneously with the application for the New Drug. Approval of the API will be considered after approval of its formulation.

Information on active ingredients

a) Drug information (Generic Name, Chemical Name or INN) & Physicochemical Data including:
b) Chemical name and Structure – Empirical formula, Molecular weight
c) Physical properties – Description, Solubility, Rotation, Partition coefficient, Dissociation constant
d) Analytical Data: Elemental analysis, Mass spectrum, NMR spectra, IR spectra, UV spectra, Polymorphic identification
e) Complete monograph specification including: Identification, Identity/ quantification of impurities, Enantiomeric purity, Assay
f) Validations: Assay method, Impurity estimation method, Residual solvent/other volatile impurities (OVI) estimation method
g) Stability Studies (refer Appendix IX of Schedule Y):
h) Final release specification,
i) Reference standard characterization,
j) Material safety data sheet.
k) Certificate of Analysis

Application of new drug should carry following data for Formulation.

2. Formulation:

i. Dosage form,
ii. Composition,
iii. Master manufacturing formula,
iv. Details of the formulation (including inactive ingredients),
v. In process quality control check,
vi. Finished product specification & Method of Analysis,
vii. Excipient compatibility study,
viii. Validation of the analytical method.
ix. Comparative evaluation with international brand(s) or approved Indian brands, if applicable.
x. Pack presentation ,
xi. Dissolution ,
xii. Assay ,
xiii. Impurities ,
xiv. Content uniformity ,
xv. PH ,
xvi. Force degradation study ,
xvii. Stability evaluation in market intended pack proposed storage conditions ,
xviii. Packing specifications ,
xix. Process validation.

3. Animal Pharmacology and Toxicity Studies

Animal Pharmacology and animal toxicology data required for IND application.

Animal Pharmacology:

  1.  Summary
  2.  Specific pharmacological actions
  3. General pharmacological actions
  4.  Follow-up and Supplemental Safety Pharmacology Studies
  5.  Pharmacokinetics: absorption, distribution; metabolism; excretion
  • General Aspects
  • Systemic Toxicity Studies
  • Male Fertility Study
  • Female Reproduction and Developmental Toxicity Studies
  • Local toxicity
  • Allergenicity/Hypersensitivity
  • Genotoxicity
  • Carcinogenicity

Animal Toxicology

1. General Aspects
2. Systemic toxicity studies,

a) Single dose toxicity
b) Repeated dose toxicity

3. Male Fertility Study
4. Female Reproduction and Developmental Toxicity Studies (for all drugs proposed to be studied or used in women of child bearing age)
5. Local toxicity

  • Dermal toxicity – for products meant for topical (dermal) application
  • Ocular toxicity – for products meant for ocular instillation
  • Inhalation toxicity – Conducted with the formulation proposed to be used via inhalation route
  • Vaginal toxicity – for products meant for topical application to vaginal mucosa
  • Photoallergy or dermal phototoxicity – Required if the drug or a metabolite is related to an agent causing photosensitivity or the nature of action suggests such a potential
  • Rectal tolerance test – For all preparations meant for rectal administration
  • Genotoxicity
  • Allergenicity/Hypersensitivity

7. Carcinogenicity – Carcinogenicity studies should be performed for all drugs that are expected to be clinically used for more than 6 months as well as for drugs used frequently in an intermittent manner in the treatment of chronic or recurrent conditions. However, completed rodent carcinogenicity studies are not needed in advance of the conduct of large scale clinical trials, unless there is a special concern for the patient population

Further the submission of requirements relating to Animal toxicology, Reproduction studies, Teratogenic Studies, Perinatal Studies, Mutagenicity and Carcinogenicity data may be modified or relaxed in case of new drugs approved and marketed for several years in other countries and adequate published evidence regarding the safety of the drug is available. Although, Drugs & Cosmetics Rules does not specifically mention about the period of marketing of a new drug in other countries which can be considered as “several years”, it may be however be clarified that for relaxation or modification of the animal toxicology data requirements of a new drug as mentioned above, the drug should be marketed in other countries for a period of more than two years and adequate evidence regarding safety of the drug in published journals should be made available to CDSCO. Such relaxation or modification of requirement of toxicological data will be considered by CDSCO on case-by-case basis in consultation with experts/experts committee.

Dr. Manoj Karwa

Auriga Research Ltd.
Email: [email protected]


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