[ANAL-LEC-MID-02] WHO GUIDELIDES

THIS FLASH CARDS IS ABOUT ANALYSIS II: GUIDELINES IN THE WORLD HEALTH ORGANIZATION (WHO).

World Health Organization (WHO)

This is the United Nations specialized agency for health.

April 7, 1948

When was the WHO established?

192 members

How many members govern the World Health Organization through the World Health Assembly?

True

True or False: All countries which are members of the United Nations may become members of WHO.

32 members

How many members of the Executive Board are technically qualified in the field of health?

3 years

The members of WHO are elected for how many years?

Director-General

Who heads the organization?

Health Assembly

Which body appoints the head of the organization?

Executive Board

Which body nominates the candidate for the position of Director-General?

• Africa

• America

• Southeast Asia

• Europe

• Eastern Mediterranean

• Western Pacific

Where are the six (6) Regional Offices of WHO?

• To give worldwide guidance in the field of health

• To set global standards for health

• To cooperate with governments in strengthening national health programs

• To develop and transfer appropriate health technology information

What are the four (4) WHO Functions?

• WHOLIS

• WHOSIS

What are the two (2) Systems of WHO?

WHO Library Database

What is the full name of WHOLIS?

WHOLIS

This system focuses on:

• Publications

• Reports

• Guidelines

• Publications

• Reports

• Guidelines

WHOLIS focuses on?

WHOLIS

The main use of this system is to access WHO documents since 1948.

1948

WHOLIS access WHO documents since when?

WHO Statistical Information System

What is the full name of WHOSIS?

WHOSIS

This system focuses on:

• Epidemiological and statistical data

Epidemiological and statistical data

WHOSIS focuses on?

WHOSIS

The main use of this system is to access health statistics and indicators.

Access health statistics and indicatiors

What is the main use of WHOSIS?

Pharmaceutical products

WHO Stability Guidelines

Guidelines for Stability Testing of _____________ containing well established drug substances in conventional dosage forms.

Conventional dosage forms

WHO Stability Guidelines

Guidelines for stability testing of pharmaceutical products containing well established drug substances in ___________________.

Final drug products

WHO Stability Guidelines

For stability of ___________ that are well established (e.g., generics) and in conventional dosage forms (e.g., tablets).

• Generics (drug products)

• Tablets (dosage forms)

WHO Stability Guidelines

What are the well established drug products and conventional dosage forms?

Reconstituted Products

“In-use” stability data must be submitted.

Reconstituted Products

“In-use” is also known as?

• Zone I: Temperate

• Zone II: Subtropical, high humidity

• Zone III: Hot/Dry

• Zone IV: Hot/Humid

What are the four (4) climatic zones?

Temperate

Zone I is also known as?

Zone I

What zone is Temperate?

Subtropical, high humidity

Zone II is also known as?

Zone II

What zones is Subtropical, high humidity?

Hot/Dry

Zone III is also known as?

Zone III

What zone is Hot/Dry?

Hot/Humid

Zone IV is also known as?

Zone IV

What zone is Hot/Humid?

• Two different production batches

• Representative of manufacturing process

• Different API batches if possible

Design of Stability Studies

What are the three (3) Test Samples?

Production batches

Design of Stability Studies

Test Samples: Two different?

Manufacturing process

Design of Stability Studies

Test Samples: Representative of?

API batches

Design of Stability Studies

Test Samples: Different __________ if possible.

• Stable formulations: one batch every other year

• Established stability: one batch every 3-5 years unless major change

Design of Stability Studies

What are the two (2) sampling schedule?

One batch every other year

Design of Stability Studies

Sampling Schedule: For stable formulations?

Stable formulations

Design of Stability Studies

Sampling Schedule: One batch every other year

One batch every 3-5 years unless major change

Design of Stability Studies

Sampling Schedule: For established stability?

Established stability

Design of Stability Studies

Sampling Schedule: One batch every 3-5 years unless major change

• Zone II: 6/3 months

• Zone IV: 6 months

• Test conditions vary

What are the Zones in Accelerated Studies?

6/3 months

In accelerated studies, how many months for Zone II?

6 months

In accelerated studies, how many months for Zone IV?

False — Test conditions varies

True or False: In accelerated studies, test conditions doesn’t vary.

Greater than 15 degrees celsius

Alternative Storage Conditions

6 months at what above expected storage temperature?

45-50 degrees celcius

Alternative Storage Conditions

3 months at what temperature?; 75% RH for Zone IV.

Intermediate conditions

Alternative Storage Conditions

What would be the condition if significant changes occur?

6 months

Alternative Storage Conditions

Real-time studies: At least how many months available at registration?

Accelerated

Frequency of Testing

0, 1, 2, 3, 6 months

0, 1, 2, 3, 6 months

Frequency of Testing

How many months for accelerated?

Real-time

Frequency of Testing

0, 6, 12 months, then yearly

0, 6, 12 months, then yearly

Frequency of Testing

How many months for real-time?

Ongoing studies

Frequency of Testing

Confirm shelf-life

Confirm shelf-life

Frequency of Testing

Ongoing studies?

Highly stable

Frequency of Testing

First 12 months, then end of shelf-life.

First 12 months, then end of shelf-life

Frequency of Testing

Highly stable?

Less table

Frequency of Testing

Every 3 months (year 1), every 6 months (year 2), then annually

Every 3 months (year 1), every 6 months (year 2), then annually

Frequency of Testing

Less stable?

Analytical methods

What are these:

• Must be validated or verified

• All product characteristics affected by storage tested

• Decomposition products tested

• Stability report includes design, results, conclusions

Validated or verified

Analytical Methods must be?

Affected by storage

Analytical Methods: All product characteristics _____________ tested.

Decomposition products

Analytical Methods: __________ products tested.

• Design

• Results

• Conclusion

Analytical Methods: Stability report includes?

n-plan (Uniform Materials)

WHO Guidelines on Sampling of Pharmaceuticals

n-plan: for uniform materials from recognized source.

• Formula: n = 1 + √N (N = sampling units)

• Random selection

• Not statistically based, only guiding principle

n-plan

For uniform materials from recognized source.

n = 1 + √N

What is the formula for n-plan?

Sampling units

In the formula, N stands for?

r-plan (Non-uniform Materials)

WHO Guidelines on Sampling of Pharmaceuticals

• Formula: r = 1.5√N

• Samples from each unit tested separately

• If results agree, pooled for retention

r = 1.5√N

What is the formula for r-plan?

n-plan

You use this plan for uniform materials from reliable sources, taking samples from a subset of containers.

r-plan

You use this plan for suspect, non-uniform materials from unknown sources, sampling from every container to identify issues before combining them for further testing, as suggested by WHO guidelines.

GMP Validation Guidelines

What are these for:

• Focuses on validation, qualification, calibration, verification

• Includes Validation Team, Master Plan, Protocol, Report, re-validation change control

• Validation

• Qualification

• Calibration

• Verification

GMP Validation Guidelines focuses on?

• Validation Team

• Master Plan

• Protocol

• Report

• Re-validation change control

GMP Validation Guidelines includes?

• Manufacturers

• Distribution channels

• Pre-approval

What are the three (3) WHO Inspection Guidelines?

• Evaluate GMP compliance

• Audit procedures

• Collect samples

What are the three (3) objectives of WHO Inspection Guidelines?

• Routine

• Concise

• Follow-up

• Special

• Investigative

What are the five (5) types of WHO Inspection Guidelines?

Mnemonics: Really Cool Friends Sheet Ice

Therapeutic equivalence

Interchangeability & Bioequivalence

Pharmaceutical is not equal to?

• Comparative bioavailability

• Pharmacodynamic

• Clinical trials

• Dissolution Tests

Interchangeability & Bioequivalence

What are the four (4) Bioequivalence Studies

Bioequivalence

Interchangeability & Bioequivalence

This is not needed for certain aqueous solutions, gases, topical solutions.

• Randomized

• Crossover

• Parallel for long half-life drugs

Interchangeability & Bioequivalence

What are the three (3) study design of BE?

90%

Interchangeability & Bioequivalence

What is the % of CI for Area Under The Curve?

Between 80-125%

Interchangeability & Bioequivalence

What is the % for Cmax?

• Log-transformation

• Minimum 12 subjects

• ANOVA

Interchangeability & Bioequivalence

What are the three (3) Statistical Considerations?