Eval Quality

8/8/2019 Eval Quality

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EVALUATION OFQUALITY OF A DRUG

PRODUCT

Prepared and presented by:

Bekele Tefera

EDM/NPO

WHO country office-Ethiopia

Work shop on Good Manufacturing Practice(GMP) & good Distribution Practices (GDP)

for domestic manufacturers, drug distributorsand dug inspectors

Nazareth, Ethiopia, 3-7 June 2002


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EDM/NPO-

Ethiopa

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Summary

One of the criteria for the scientificassessment of a drug product is quality.

Application for registration of a new productmust be accompanied by the followingquality assurance data:

Development pharmaceutics

Qualitative & quantitative composition of

the dosage form (including excepients) Method of manufacture of the dosage

form

Specifications of all the ingredients andthe finished dosage form

Analytical methods

Stability data (stability study results)


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EDM/NPO-

Ethiopa

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The above quality assurance data

serve as a basis for evaluation of the

quality of a drug product.

Laboratory analysis / qualitycontrol is the cap stone for the

evaluation of a drug product for

registration.

Some of the above quality

assurance data will be

discussed in detail below.


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EDM/NPO-

Ethiopa

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Development

Pharmaceutics Related to the different stages of

new drug development

Can be grouped in to two:Pre formulation

Formulation

Pre formulation A phase of aresearch and development processwhere the pre formulation scientistcharacterizes the physical,

chemical and mechanicalproperties of a new drug substancein order to develop stable, safe andeffective dosage forms.


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EDM/NPO-

Ethiopa

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Formulation

the composition of a dosage

form, including the

characteristics of its row

materials and operations

required to process it.


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EDM/NPO-

Ethiopa

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Stages of new drug

development

Research

concept &

discovery of

lead

compound

Pre clinical testing

Clinical testing

Registration

with DRALaunch & Sale


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EDM/NPO-

Ethiopa

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Pharmacy and chemical

development works at

each research phaseI Research concept and discovery

of active lead compound

(Involves 8,000-10,000 potential candidate substances)

Focuses mainly onextraction/synthesis of activesubstances at laboratory scale

II Preclinical testing1 Selection of product candidate

(basic pharmacology/biochemicalscreening) (20-30 substances reach thisstage)

Analytical characterization ofactive substances is the maintask


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EDM/NPO-

Ethiopa

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2 Biological testing

(pharmacological/toxicological

studies)

(5-10 substances reach this stage)

Development of specific analytical

methods of active substances, theirdegradation products and possible

contaminants

Pre formulation studies to

determine formulation constraints

and possibilities

Synthesis of active substances at

technical scale Consideration of alternative routes

of synthesis of active substances


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EDM/NPO-

Ethiopa

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Preparation of model formulation for

clinical and toxicological evaluation

Synthesis of radio labeledcompound for pharmacokinetic

studies Development of analytical

methodology

Stability testing of activesubstances and modelformulation

Production of formulation of

active substances andcomparison formulation forclinical trials


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EDM/NPO-

Ethiopa

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III Clinical trials ( phase I-II )

(Approximately 4-5 substances remain)

Scale up of synthesis to pilot plant

D

evelopment of analytical methods forQ.C testing

Development of variety of formulationse.g. tablet, capsules, injections, etc

Development of process of manufacture

of formulation Design of chemical manufacturing plant

Design of process of secondarypharmaceutical manufacture

Confirmation of stability of products in thefinal packs

Validation and finalization of Q.Cmethodology and specifications


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EDM/NPO-

Ethiopa

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IV Registration with health

authorities

(1 substance remain )

Design and preparation ofpackaging materials

Construction/commissioning ofchemical plant at full scale

Validation of manufacturing

process Development of quality

assurance , in-process controlprocedures

Construction andcommissioning of secondarymanufacturing units


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EDM/NPO-

Ethiopa

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V Launch and sales

Scheduling , ordering

Production of final dosageform, packaging and product

literature

Quality control for release of

products


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EDM/NPO-

Ethiopa

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OTHER QUALTY

ASSURANCE DATA

Specifications

Describe in detail the requirementswith which products or materialsused or obtained duringmanufacturing have to conform.

They serve as yard sticks forquality evaluation

Sources of specifications

Pharmacopeal

In-house


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EDM/NPO-

Ethiopa

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Types of specifications

Raw material specifications

Container closurespecifications

Finished product specifications

Finished product specifications

Release specifications

Stability indicating specifications


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EDM/NPO-

Ethiopa

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Release specifications

The combinations of physical, chemical,

biological and microbiological test

requirements that determine whether adrug product is suitable for release at the

time of manufacture.

Stability indicating specifications

The combination of physical, chemical,

biological and microbiological test

requirements that the active ingredients

or a drug product must meet during its

shelf life


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EDM/NPO-

Ethiopa

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EXAMPLES OF

SPECIFICATIONS

Active pharmaceutical ingredients

Identity

Purity

Content

Physico chemical properties such

as solubility, melting points, particle

size, etc.

PH


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EDM/NPO-

Ethiopa

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Finished product

specifications

General

Organoleptic properties

(appearance, color, odor)

Identification Purity

PH

Moisture content Abnormal toxicity


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EDM/NPO-

Ethiopa

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Specific

Tablet dissolution/disintegration,

weight variation, uniformity of

content, friability, hardness, etc

Capsules dissolution/disintegration,

weight variation, brittleness, etc

Injectables- Clarity, PH, sterility,

pyrogen test (LVP), Volume, etc.

Ophthalmic products- PH, sterility,

weight variation, etc


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EDM/NPO-

Ethiopa

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2. The analytical method must

be validated in terms of:

Accuracy

Precision (Repeatability,intermediate precision,

reproducibility)

Specificity

Sensitivity (limit of detection,

limit of quantification)

Linearity

Range

Robustness


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EDM/NPO-

Ethiopa

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REFERENCES

1. Commission of the European community (1989) :The rules governing medicinal products in theEuropean community: Guide to Good manufacturingPractice of medicinal products; office for official

publications of the European communities;

2. Gennaro A.R (1995): Remington's pharmaceuticalscience, 19th edition; Mack publishing Co. , USA;

3. Gilman, AG (1990): The pharmacological basis oftherapeutics, 8th edition. Macmillan publishing Co.,

USA;

3. ICH (1994): HarmonizedTripartite guideline-Text onvalidation of analytical procedures; recommendationfor adoption at step 4 of the ICH process on 27October 1994 by the steering committee

4. The British Pharmacopeal Commission (2000):British Pharmacopoeia;


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EDM/NPO-

Ethiopa

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5. The united states Pharmacopea

commission(2000): The united States

Pharmacopea (USP 24) and National

Formulary (N

F19);

6. US FDA (1990): From test tube to patient: New

drug development in the United States. USA:

Department of Health and Human Services. An

FDA consumer special report. DHS publicationNo. 90-3168

7. WHO(1999): Marketing authorization of

pharmaceutical products with special referenceto multi source (generic) products,

WHO/DMP/PRGS/98.5

Documents

Eval Quality