Professional Documents
Culture Documents
Qa &ra
Qa &ra
Qa &ra
Quality control, assurance and management of various parameters for achieving quality
pharmaceutical products.
This course deals with the basic need of quality in the manufacturing of Pharmaceutical
products and it's build up with the help of quality control and quality assurance management.
This course also covers the regulatory procedures applicable in clinical trials and approval of
new drug products
Understanding the regulations, requirements, procedures and applications of new drug approval
process
Introduction
Points to cover
Concepts and tools in the planning, implementation and control of current Good Manufacturing
Practices in the Pharmaceutical industry
Points to cover
Quality audit (means and mechanism) as a tool for manufacturing and quality control system
development
Quality Audit
ISO certification
Points to cover
Concepts, tools, methods and statistical application in validation of various areas in a Pharmaceutical
industry
Organization
Prospective validation
OR
A chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to
otherwise enhance physical or mental well-being.
The process by which new chemicals that might have specific biological activity are
developed.
The chemicals are examined to see if they are active using some assay or biological
marker to determine if they might be useful clinically.
Goals of Drug Discovery
To develop a drug that will benefit patients, satisfy prescribers and earn profits for the
company.
Drug development is not always successful, but when it does lead to a new drug
available to patients and doctors, it is a very satisfying endeavor.
Reasons for Medication Use
Prevention
Vaccines
Antimalaria agents
Antibiotic prophylaxis
Curative
Antibacterial
Oncology drugs
Antifungal
Control of Disease Process
Antihypertensives
Antidiabetics
Thyroid agents
Palliation
Analgesics
Oncology drugs
Life Cycle of a Drug:
The approximate cost of developing a new drug, from the concept to the market is
approx. US$1000+ million
Therefore the process of drug discovery is fraught with great uncertainty and financial
burden
For every 10000 chemicals screened, only 1000 show some biological activity
The approximate cost of developing a new drug, from the concept to the market is
approx. US$1000+ million
Therefore the process of drug discovery is fraught with great uncertainty and financial
burden
Ensuring Drugs Are Safe and Effective
The path a drug travels from a lab to your medicine cabinet is usually long, and every drug
takes a unique route.
Often, a drug is developed to treat a specific disease.
An important use of a drug may also be discovered by accident- Penicillin.
Retrovir (zidovudine, also known as AZT) was first studied as an anti-cancer drug in the
1960s with disappointing results.
Twenty years later, researchers discovered the drug could treat AIDS, and Food and Drug
Administration approved the drug, manufactured by GlaxoSmithKline, for that purpose in
1987.
Most drugs that undergo preclinical (animal) testing never even make it to human testing and
review by the FDA.
Drugs must undergo the agency's rigorous evaluation process
which scrutinizes everything about the drug--from the design of clinical trials
to the severity of side effects to the conditions under which the drug is
manufactured.
Stages of Drug Development and Review
Sponsors--companies, research institutions, and other organizations that take responsibility
for developing a drug- Target Identification.
They must show the FDA results of preclinical testing in laboratory animals and what they
propose to do for human testing.
At this stage, the FDA decides whether it is reasonably safe for the company to move forward
with testing the drug in humans.
Pre-clinical Studies
Extensive Toxicological Tests and Animal Experiments are conducted to determine
efficacy and safety of the compound to predict its efficacy and safety in Humans.
They are conducted to ascertain that the drug may be tested safely in Human and may
be effective in specific Human Disease state.
Objectives of Pre-clinical Studies
Predict Human Efficacy
Pharmacodynamics (PD)
Primary Pharmacodynamics: studies on mode of action and/or effects of a
substance to its desired therapeutic effects
Secondary Pharmacodynamics: effects of a substance not related to its desired
therapeutic target
Safety pharmacology (S7A and S7B ICH guideline)
Specific molecular markers are characteristic of particular cancer types. IHC is also
widely used in basic research to understand the distribution and localization of
biomarkers in different parts of a tissue
Visualizing an antibody-antigen interaction can be accomplished in a number of ways
The proteins are then transferred out of the gel and onto a membrane (typically
nitrocellulose), where they are "probed" using antibodies specific to the protein.
As a result, researchers can examine the amount of protein in a given sample and
compare levels between several groups
Animal Toxicity Studies
Immunotoxicity (S8 ICH guideline)
Systemic Toxicity Studies (S4 ICH guideline)
Single Dose
Repeated Dose
Local Toxicity Studies (S4 ICH guideline)
Specialized toxicity studies
Male fertility Studies (S5 ICH guideline)
Female reproduction and fetal development (Teratogenecity) (S5)
Carcinogenicity (S1A-S1C ICH guideline)
Genotoxicity (S2 ICH guideline)
Safety Evaluation Information
Starting dose
Ethical and scientific justification to expose human to new drug and helps to plan the
clinical trials
Preclinical trial data is one of the requirements used for Investigational New drug
application submission
Basic process for a new drug approval
Its an application filed to the FDA in order to start clinical trials in humans if the drug was
found to be safe from the reports of Preclinical trials. A firm or institution, called a Sponsor,
is responsible for submitting the IND application.
If clinical studies confirm that a new drug is relatively safe and effective, and will not pose
unreasonable risks to patients, the manufacturer files a New Drug Application (NDA), the
actual request to manufacture and sell the drug.
Abbreviated New Drug Application (ANDA)
Its an application made for approval of Generic Drugs. Generic drug manufacturers must
demonstrate that their product is the same as, and bioequivalent to, a previously approved
brand name product.
Its an application filed to the FDA in order to start clinical trials in humans if the drug was
found to be safe from the reports of Preclinical trials. A firm or institution, called a Sponsor,
is responsible for submitting the IND application.
Clinical Trials
Drug studies in humans can begin only after an IND is reviewed by the FDA and a local
institutional review board (IRB).
The board is a panel of scientists and non-scientists in hospitals and research institutions that
oversees clinical research.
IRBs approve the clinical trial protocols, which describe the type of people who may
participate in the clinical trial, the schedule of tests and procedures, the medications and
dosages to be studied, the length of the study, the study's objectives, and other details.
During a new drug's early preclinical development, the sponsor's primary goal is to:
the sponsor then focuses on collecting the data and information necessary to
establish that the product will not expose humans to unreasonable risks when
used in limited, early-stage clinical studies.
FDA's role in the development of a new drug begins when the drug's sponsor (usually
the manufacturer or potential marketer), having screened the new molecule for
pharmacological activity and acute toxicity potential in animals, wants to test its
diagnostic or therapeutic potential in humans.
At that point, the molecule changes in legal status under the Federal Food, Drug, and
Cosmetic Act and becomes a new drug subject to specific requirements of the drug
regulatory system.
Must be an individual
Types of IND
An Investigator IND:
It is also used for patients who do not meet the criteria of an existing study
protocol, or if an approved study protocol does not exist.
Classification of IND
Commercial
o Permits sponsor to collect data on clinical safety and effectiveness needed for
application for marketing in the form of NDA
Research (non-commercial)
Also included are any previous experience with the drug in humans
2. Manufacturing Information -
Detailed protocols for proposed clinical studies to assess whether the initial-
phase trials will expose subjects to unnecessary risks.
IND Application
Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any
clinical trials.
During this time, FDA has an opportunity to review the IND for safety to assure that research
subjects will not be subjected to unreasonable risk.
Format of IND
o Identification of phases
o Signature of sponsor
B. Table of contents
D. Investigators brochure
E. Study protocol
312.2 Applicability.
312.3 Definitions and interpretations.
312.10 Waivers.
312.1 Scope
This part contains procedures and requirements governing the use of investigational new
drugs, including procedures and requirements for the submission to, and review by, the Food
and Drug Administration of investigational new drug applications (INDs).
An investigational new drug for which an IND is in effect in accordance with this part is
exempt from the premarketing approval requirements that are otherwise applicable and may
be shipped lawfully for the purpose of conducting clinical investigations of that drug
312.3 Definitions and interpretations.
Contract research organization:
means a person that assumes, as an independent contractor with the sponsor,
one or more of the obligations of a sponsor, e.g., design of a protocol,
selection or monitoring of investigations, evaluation of reports, and
preparation of materials to be submitted to the Food and Drug Administration.
Clinical investigation:
means any experiment in which a drug is administered or dispensed to, or used
involving, one or more human subjects.
312.3 Definitions and interpretations.
Investigator:
Investigator means an individual who actually conducts a clinical investigation
(i.e., under whose immediate direction the drug is administered or dispensed to
a subject).
In the event an investigation is conducted by a team of individuals, the
investigator is the responsible leader of the team.
Subinvestigator includes any other individual member of that team., or used
involving, one or more human subjects.
312.3 Definitions and interpretations.
Subject:
Subject means a human who participates in an investigation, either as a
recipient of the investigational new drug or as a control.
A subject may be a healthy human or a patient with a disease.
312.3 Definitions and interpretations.
Sponsor:
Sponsor means a person who takes responsibility for and initiates a clinical
investigation.
The sponsor may be an individual or pharmaceutical company, governmental
agency, academic institution, private organization, or other organization.
The sponsor does not actually conduct the investigation unless the sponsor is a
sponsor-investigator.
Subpart BInvestigational New Drug
Application (IND)
312.20 Requirement for an IND.
312.2 Applicability.
312.10 Waivers.
312.1 Scope
This part contains procedures and requirements governing the use of investigational new
drugs, including procedures and requirements for the submission to, and review by, the Food
and Drug Administration of investigational new drug applications (INDs).
An investigational new drug for which an IND is in effect in accordance with this part is
exempt from the premarketing approval requirements that are otherwise applicable and may
be shipped lawfully for the purpose of conducting clinical investigations of that drug
312.3 Definitions and interpretations.
Contract research organization:
means a person that assumes, as an independent contractor with the sponsor,
one or more of the obligations of a sponsor, e.g., design of a protocol,
selection or monitoring of investigations, evaluation of reports, and
preparation of materials to be submitted to the Food and Drug Administration.
Clinical investigation:
means any experiment in which a drug is administered or dispensed to, or used
involving, one or more human subjects.
312.3 Definitions and interpretations.
Investigator:
Investigator means an individual who actually conducts a clinical investigation
(i.e., under whose immediate direction the drug is administered or dispensed to
a subject).
In the event an investigation is conducted by a team of individuals, the
investigator is the responsible leader of the team.
Subinvestigator includes any other individual member of that team., or used
involving, one or more human subjects.
312.3 Definitions and interpretations.
Subject:
Subject means a human who participates in an investigation, either as a
recipient of the investigational new drug or as a control.
A subject may be a healthy human or a patient with a disease.
312.3 Definitions and interpretations.
Sponsor:
Sponsor means a person who takes responsibility for and initiates a clinical
investigation.
The sponsor may be an individual or pharmaceutical company, governmental
agency, academic institution, private organization, or other organization.
The sponsor does not actually conduct the investigation unless the sponsor is a
sponsor-investigator.
Subpart BInvestigational New Drug
Application (IND)
312.20 Requirement for an IND.