Quality In Investigational Drugs

Presented by: Larry Parker, BSMT (ASCP), MHSA,

ASQ CQA

American Society for Quality Central Arkansas Section 1407

What do you expect from the medicines that you take?

What do you expect from the medicines that you take?• Expect them to work.

What do you expect from the medicines that you take?• Expect them to work.• Expect them to be safe.

How does FDA make sure that medicines used in the United States are safe and effective?

How does FDA make sure that medicines used in the United States are safe and effective?• Regulations based on scientific quality.

How does FDA make sure that medicines used in the United States are safe and effective?• Regulations based on scientific quality.• Inspections based on the regulations.

How does FDA make sure that medicines used in the United States are safe and effective?• Regulations based on scientific quality.• Inspections based on the regulations.• Enforcement actions for companies and

individuals based on public health law.

Safety First

The first thing FDA requires is that you show a drug product is safe.

Safety First

The first thing FDA requires is that you show a drug product is safe.• FDA will almost always require that there are

animal safety studies done before a new drug can be given to a human.

Safety First

The first thing FDA requires is that you show a drug product is safe.• FDA will almost always require that there are

animal safety studies done before a new drug can be given to a human.

• Animal studies are regulated under the Good Laboratory Practices (GLPs) found in 21 CFR 58

Safety First

Quality in the GLPs is insured in the following ways:

Safety First

Quality in the GLPs is insured in the following ways:1. Facilities that conduct GLP studies must allow

FDA to inspect them.

Safety First

Quality in the GLPs is insured in the following ways:1. Facilities that conduct GLP studies must allow

FDA to inspect them.2. Each animal facility must have a quality

assurance unit that inspects all it studies

Safety First

Quality in the GLPs is insured in the following ways:1. Facilities that conduct GLP studies must allow

FDA to inspect them.2. Each animal facility must have a quality

assurance unit that inspects all it studies3. Written protocols are followed by the facility

for the conduct of each study

Safety First

Quality in the GLPs is insured in the following ways:1. Facilities that conduct GLP studies must allow

FDA to inspect them.2. Each animal facility must have a quality

assurance unit that inspects all it studies3. Written protocols are followed by the facility for

the conduct of each study4. Equipment used in each study is validated for

use in the study prior to the start of the study

Safety First: On to humans

Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review.

Safety First: On to humans

Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review.INDs contain:• The clinical protocol that is intend for use in

humans

Safety First: On to humans

Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review.INDs contain:• The clinical protocol that is intend for use in

humans• Animal Safety Data

Safety First: On to humans

Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review.INDs contain:• The clinical protocol that is intend for use in

humans• Animal Safety Data• Drug product manufacturing information

Safety First: On to humans

Before FDA will allow use of a new drug in human studies you must file an Investigational New Drug (IND) application for their review.INDs contain:• The clinical protocol that is intend for use in

humans• Animal Safety Data• Drug product manufacturing information• All references intended to support the application

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?• Identity

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?• Identity• Strength

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?• Identity• Strength• Potency

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?• Identity• Strength• Potency• Purity

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?• Identity• Strength• Potency• Purity• Quality

INDs

What does FDA expect you to know about a new drug that is going to be used in Humans?• Identity• Strength• Potency• Purity• Quality

Everything!

GMPs

You know everything about a investigational drug product based on the Good Manufacturing Practice Regulations (cGMPs) found in 21 CFR 210 & 211

GMPs

The GMPs:• Define the responsibilities of a companies

Quality Control Unit

GMPs

The GMPs:• Define the responsibilities of a companies

Quality Control Unit• Define the minimum qualifications for QA

personnel

GMPs

The GMPs:• Define the responsibilities of a companies

Quality Control Unit• Define the minimum qualifications for QA

personnel• Define the minimum specifications for

facilities and equipment

GMPs

The GMPs:• Define the responsibilities of a companies

Quality Control Unit• Define the minimum qualifications for QA

personnel• Define the minimum specifications for facilities

and equipment• Provide requirements for control of

components and products

GMPs

The GMPs:• Define the responsibilities of a companies Quality Control

Unit• Define the minimum qualifications for QA personnel• Define the minimum specifications for facilities and

equipment• Provide requirements for control of components and

products• Provide for controls on processing, production, packaging,

labeling, holding, and distribution of drug product

GMPsThe GMPs:• Define the responsibilities of a companies Quality Control

Unit• Define the minimum qualifications for QA personnel• Define the minimum specifications for facilities and

equipment• Provide requirements for control of components and

products• Provide for controls on processing, production, packaging,

labeling, holding, and distribution of drug product• Also provides minimum requirements for laboratory

controls, records and reports

But does it work?

But does it work?

• Phase II clinical trials involve drugs that have successfully completed safety testing and start to look and see if a drug is effective and why it is effective.

But does it work?

• Phase II clinical trials involve drugs that have successfully completed safety testing and start to look and see if a drug is effective and why it is effective.

• Phase III clinical trials use all the information found in the earlier phases and expand it to large numbers of subjects in different locations to verify that the data is still the same.

Marketing a drug

• After you have completed the Phase III trials you can file for marketing clearance with FDA in order to be able to sell the drug.

Marketing a drug

• After you have completed the Phase III trials you can file for marketing clearance with FDA in order to be able to sell the drug.

• Quality doesn’t stop there! FDA requires “post-marketing” studies usually called Phase IV studies that are on going as long as the drug is on the market.

Questions:

Quality Workshop

Quality By Design:

What is QbD?

What is QbD?

• FDA push to improve the drug development process

What is QbD?

• FDA push to improve the drug development process

• Seeks to reduce the cost of product development due to low efficiencies, waste, and manufacturing time requirements due to testing

What is QbD?

• FDA push to improve the drug development process

• Seeks to reduce the cost of product development due to low efficiencies, waste, and manufacturing time requirements due to testing

• FDA states that you can’t test quality into a product, it must be designed there

What is QbD?

• A scientific, risk-based, holistic and proactive approach to pharmaceutical development.

What is QbD?

• A scientific, risk-based, holistic and proactive approach to pharmaceutical development.

• A deliberate design effort from product conception through commercialization.

What is QbD?

• A scientific, risk-based, holistic and proactive approach to pharmaceutical development.

• A deliberate design effort from product conception through commercialization.

• Manufacturer’s should have a full understanding of how product attributes and process relate to product performance

QbD System

Better View

Another Flow Chart