GUIDELINE FOR APPLICANTS AND MODEL APPLICATION FORM IN ETHIOPIA

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GUIDELINE FOR APPLICANTS AND MODEL APPLICATION
FORM IN ETHIOPIA

• Prepared and presented by
• Bekele Tefera
  EDM/NPO
• WHO country office-Ethiopia
• Work shop on Good Manufacturing Practice (GMP)
  and Good Distribution Practice (GDP) for domestic
  manufacturers, drug distributors and drug
  inspectors
• Nazareth, Ethiopia, 3-7 June 2002

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General

• DRAs prepare registration guideline
• Applicants are expected to comply with these
  guidelines.
• Principal criteria of registration
• Safety
• Efficacy
• Quality
• Labeling requirements

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Strategies of drug evaluation

• Documentary evaluation
• Laboratory analysis
• Important terms
• Efficacy the ability to produce the purported
  effect as determined by scientific methods
• Safety- the absence of an unaccepted harmful
  effects (i.e. negative risk/benefit ratio) of a
  drug to the health of the consumer when used
  according to the instructions on/or enclosed in
  the package.

4
Quality

• The nature of a drug determined by identity,
  content, purity, and other chemical, physical and
  biological properties or by the manufacturing
  process.
• New product- is a product containing
• New chemical entity
• New salts and esters of an active ingredient
• New fixed combinations
• New indication
• new dosage form

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Types of registration applications

• New Drug Application (NDA)
• Abbreviated New Drug Application (ANDA)
• Various other forms of application including
• Re registration
• Change of origin
• Change of pack size
• Change of container closure
• Change in formulation
• Change in the production process
• Change in quality specifications/quality control
  method

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Requirements for ANDA

• An ANDA is an application for the registration of
  a product containing an active ingredient which
  has been used extensively and for which
  sufficient evidence exists to demonstrate its
  safety and efficacy (i.e. generic product)
• Such kind of application should be accomplished
  by the following administrative data and
  technical data

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Administrative data

• Application form
• Agency agreement
• WHO-type Certificate of pharmaceutical products (
  for manufacturers abroad)
• Manufacturing license (for domestic
  manufacturers)
• Registration fee

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Technical data

• Quality
• Data on active ingredient
• Non propriety name
• Molecular formula
• Structure
• Synthesis
• Physico chemical properties
• Stability
• Key raw materials
• Key intermediates
• Degradation profile
• Quality specifications
• Test methods

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Method of manufacture of the finished product
showing

• Qualitative quantitative composition
• Batch manufacturing formula
• In-process quality control
• Data on container-closure
• Process validation information

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Analytical Report

• Quality specifications
• Analytical methods
• Validation information
• Stability study report
• Results of a study on at least two batches
• Batch NO. Manufactory date expiry date
• Nature of container closure
• Storage condition (T0, R?H, Light, etc)
• Results of test parameters at each test interval
  (for real time studies at 0,3,6,12,24,36, etc
  months)
• For accelerated stability studies a maximum of 6
  months data
• Data on degradation products
• Proposed storage conditions and shelf life

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Laboratory analysis

• Samples of actual products are required for
  laboratory analysis
• Efficacy
• Assumed to have been established
• In vivo bioequivalence data

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Labeling information

• Drug product chemical Information
• Package insert
• Label of the immediate container
• Outer wrapper or carton

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Package insert

• Must show
• Name of the product (INN)
• Description
• Composition
• Clinical pharmacology
• Warnings, precautions, contraindications
• Adverse effects
• Dosage administration
• Over dosage
• Potential of drug abuse and dependence
• How supplied
• Name and address of the manufacturer
• Date of the last review

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Label of the immediate container

• Should show
• Name of the product (INN)
• Pharmaceutical form
• Composition
• Quantity in container
• Technical direction
• Contraindications, warnings, precautions
• Storage conditions
• Manufactory date and expiry date
• Batch number
• Name and address of the manufacturer

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Outer wrapper or carton

• Must bear all the information enumerated under
  package inserts

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New drug Application

• An NDA is an application for the registration of
  a new product as defined above and such kind of
  application must be accompanied by the following
  administrative data.
• Quality
• All the quality data enumerated under abbreviated
  drug application
• Efficacy
• In vitro models

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Animal pharmacology

• Pharmaco dynamic
• Pharmacokibnetic
• Clinical study results
• Clinical pharmacology (pharmacodynamic/kinetic)
• Bioavailability study
• Clinical trial results
• (Phase I,II,II)

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Safety

• Toxicological studies including
• Acute toxicity
• Sub acute toxicity and chronic toxicity
• Reproductive and teratology
• Fertility
• Embryo toxicity/teratology
• Perinatal and post natal studies
• Carcinogenicity
• Labeling information
• As indicated for ANDA

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REFERENCES

• CIOM (1983) Safety requirements for the first
  use of new drugs and diagnostic agents in man.
  Geneva CIOM. A review of safety issues in early
  clinical trials of drugs
• Ministry of Health of Ethiopia (1996)
  Consolidated guidelines on the requirements for
  the registration of products and manufacturing
  companies
• WHO (1985) Draft guideline on the requirements
  for registration of drugs. WHO-Eastern
  Mediterranean region. WHO-EDM (PHARM?105)
• WHO (1975) Guidelines for evaluation of drugs
  for use in man. Geneva WHO. Scientific group WHO
  technical report series No. 563