GUIDELINE FOR APPLICANTS AND MODEL APPLICATION FORM IN ETHIOPIA

1. 1 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

2. Bekele Tefra, EDM/NPO, Ethiopia 2 General DRAs prepare registration guideline Applicants are expected to comply with these guidelines. Principal criteria of registration Safety Efficacy Quality Labeling requirements

3. Bekele Tefra, EDM/NPO, Ethiopia 3 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. Bekele Tefra, EDM/NPO, Ethiopia 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

5. Bekele Tefra, EDM/NPO, Ethiopia 5 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

6. Bekele Tefra, EDM/NPO, Ethiopia 6 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:

7. Bekele Tefra, EDM/NPO, Ethiopia 7 Administrative data Application form Agency agreement WHO-type Certificate of pharmaceutical products ( for manufacturers abroad) Manufacturing license (for domestic manufacturers) Registration fee

8. Bekele Tefra, EDM/NPO, Ethiopia 8 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

9. Bekele Tefra, EDM/NPO, Ethiopia 9 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

10. Bekele Tefra, EDM/NPO, Ethiopia 10 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

11. Bekele Tefra, EDM/NPO, Ethiopia 11 Laboratory analysis Samples of actual products are required for laboratory analysis Efficacy Assumed to have been established In vivo bioequivalence data

12. Bekele Tefra, EDM/NPO, Ethiopia 12 Labeling information Drug product = chemical + Information Package insert Label of the immediate container Outer wrapper or carton

13. Bekele Tefra, EDM/NPO, Ethiopia 13 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

14. Bekele Tefra, EDM/NPO, Ethiopia 14 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

15. Bekele Tefra, EDM/NPO, Ethiopia 15 Outer wrapper or carton Must bear all the information enumerated under package inserts

16. Bekele Tefra, EDM/NPO, Ethiopia 16 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

17. Bekele Tefra, EDM/NPO, Ethiopia 17 Animal pharmacology Pharmaco dynamic Pharmacokibnetic Clinical study results Clinical pharmacology (pharmacodynamic/kinetic) Bioavailability study Clinical trial results (Phase I,II,II)

18. Bekele Tefra, EDM/NPO, Ethiopia 18 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

19. Bekele Tefra, EDM/NPO, Ethiopia 19 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