TOPIC 1: PHARMACEUTICAL DOSAGE FORMS, DRUG DELIVERY SYSTEMS AND MEDICAL DEVICES

Drugs

agents used for the diagnosis, mitigation, treatment, cure or prevention of diseases in humans or animals.

Prescription drugs

requires a healthcare provider authorization

drugs

One of the astounding qualities of … is the diversity of their actions and effects on the body. This quality enables their selective use in the treatment of a range of common and rare conditions involving virtually every body organ, tissue and cell.

OTC (over- the- counter) drugs

available without prescription

Herbal and natural remedies

Derived from plants and other natural sources

for digestion, cancer, nervous system

Diverse reaction and effects on the body

Therapeutic

Preventive

Diagnostic

Roles of drugs

Therapeutic

alleviate symptoms or cure diseases

Preventive

vaccine and prophylactic treatments

Diagnostics

used in medical tests and imaging

X-rays

MRI

Citi scan

examples of diagnostic

First apothecary

Before the days of the priestcraft, the wise man or woman of the tribe, whose knowledge of the healing qualities of plants has been gathered through experience or handed down by word of mouth was called upon to attend to the sick or wounded and prepare the remedy. It was in the preparation of the medicinal materials that the art of the apothecary originated.

Early drugs

Because of the patience and intellect of the archaeologist, the types and specific drugs used in the early history of drug therapy are not as indefinable as one might suspect. Numerous ancient tablets, scrolls, and other relics as early as 3000 bc have been uncovered and deciphered by archaeologic scholars to the gratitude of historians of both medicine and pharmacy

pharmacopeia or formularies

Organized set of monographs or books of these standards are called

Prophylaxis

so that the progress of condition will not continue

Early research

As the knowledge of the basic sciences increase, so did their application to pharmacy. The opportunity was presented for the investigation of medicinal materials on a firm scientific basis, and the challenge was accepted by numerous pharmacists who conducted their research in the back. Rooms and basements of their pharmacies

Drug Standards

As the scientific basis for drugs and drug products developed, so did the ned for uniform standards to ensure quality. This need led to the development and publication of monographs and reference books containing such standards to be used by those involved in the production of drugs and pharma products. Organized set of monographs or books of these standards are called pharmacopeia or formularies

Pharmaceutics

study of preparations of drug dosage fork and drug delivery systems with their use in patient care

Pharmaceutics

It is a branch of pharmacy that include the study of formulation of drug into dosage forms

Dosage form

mean through which drugs are delivered in the body towards its site of action

Pharmaceutics

It provides the knowledge of interrelationship between physical pharmacy, bio pharmaceutics, pharmacokinetics, dosage form design, formulation, small and large scale manufacture and the clinical application of dosage forms in patient care

Dosage form

includes drug and pharmaceutical excipient

Dosage forms

They are the final product containing drugs that is administered to the patients

Medical devices

can be any instrument, apparatus, implement, machine, appliance, implant, reagent for in vitro use, software, material or other similar or related article, intended by the manufacturer to be used, alone or in combination for a medical purpose.

Dosage forms

Includes active drug and pharmaceutical excipient

Discovery and development

Preclinical research

Clinical research

FDA review

FDA- Post Market Safety Monitoring

Drug development process

Discovery

Typically, researchers discover new drugs through:

New insights into a disease process that allow researchers to design a product to stop or reverse the effects of the disease.

Many tests of molecular compounds to find possible beneficial effects against any of a large number of diseases.

Existing treatments that have unanticipated effects.

New technologies, such as those that provide new ways to target medical

Development

Once researchers identify a promising compound for development, they conduct experiments to gather information on:

How it is absorbed, distributed, metabolized, and excreted.

Its potential benefits and mechanisms of action.

The best dosage.

The best way to give the drug (such as by mouth or injection).

Side effects or adverse events that can often be referred to as toxicity.

How it affects different groups of people (such as by gender, race, or ethnicity) differently.

How it interacts with other drugs and treatments.

Its effectiveness as compared with similar drugs.

Tylenol- 650 mg (International)

Internation proffered painkiller

Paracetamol 500mg

Philippines preferred painkiller

In Vitro

Latin for "in glass," refers to biological processes performed outside a living organism, typically in a controlled laboratory environment (e.g., in test tubes or petri dishes).

In vivo

Latin for "within the living," refers to experiments or studies conducted in living organisms, such as animals or humans.

FDA

requires researchers to use good laboratory practices (GLP), defined in medical product development regulations, for preclinical laboratory studies.

Clinical Research

Clinical research” refers to studies, or trials, that are done in people. As the developers design the clinical study, they will consider what they want to accomplish for each of the different Clinical Research Phases and begin the Investigational New Drug Process (IND), a process they must go through before clinical research begins.

Investigational New Drug Process (IND)

a process they must go through before clinical research begins.

•study conduct

•personnel

•facilities

•equipment

•written protocols

•operating procedures

•study reports

•and a system of quality assurance oversight for each study to help assure the safety of FDA- regulated product

These regulations set the minimum basic requirements for

Investigational New Drug (IND)

Drug developers, or sponsors, must submit an_ application to FDA before beginning clinical research

Animal study data and toxicity (side effects that cause great harm) data

Manufacturing information

Clinical protocols (study plans) for studies to be conducted

Data from any prior human research

Information about the investigator

In the IND application, developers must include:

Phase 1

Study Participants: 20 to 100 healthy volunteers or people with the disease/condition.

Length of Study: Several months

Purpose: Safety and dosage

Approximately 70% of drugs move to the next phase

preclinical studies

Usually, are not very large. However, these studies must provide detailed information on dosing and toxicity levels. After _ testing, researchers review their findings and decide whether the drug should be tested in people.

Phase 2

Study Participants: Up to several hundred people with the

disease/condition.

Length of Study: Several months to 2 years

Purpose: Efficacy and side effects

Approximately 33% of drugs move to the next phase

Phase 3

Study Participants: 300 to 3,000 volunteers who have the disease or condition

Length of Study: 1 to 4 years

Purpose: Efficacy and monitoring of adverse reactions

Approximately 25-30% of drugs move to the next phase

Phase 4

Study Participants: Several thousand volunteers who have the disease/condition

Purpose: Safety and efficacy

Current Good Manufacturing Practice

refers to a system that ensures products are consistently produced and controlled according to quality standards to ensure that medicines are manufactured to the highest quality for safety and efficacy and to minimize the risks involved in production

GMP

By adhering to _, manufacturers can ensure that their products are safe, fit for their intended use, and meet the required quality standards

GMP

The significance of _ lies primarily in ensuring the safety and efficacy of drugs and _ compliance is non-negotiable.

It sets out requirements for documentation, personnel qualifications, sanitation, equipment verification, process validation, and complaint handling.

GMP helps minimize risks involved in pharmaceutical production such as cross-contamination, mix-ups, and deviations.

regulatory bodies (FDA)

GMP regulations are enforced by

GMP regulations

Non-compliance with _ can result in severe penalties

Implementing GMP

_ in pharmaceutical manufacturing is a proactive process that involves establishing systems for recording, validating, and monitoring manufacturing processes

Quality Assurance

plays a pivotal role in implementing GMP

GMP certification

demonstrates a company’s commitment to producing safe and high-quality products

GMP training programs

equip individuals with the knowledge and skills necessary for maintain GMP compliance

quality management systems, process validation, risk management, and change control

Programs cover various aspects of GMP such as

Current Good Manufacturing Practice

are established by the Food and Drug Administration (FDA) to ensure that minimum standards are met for drug product quality in the United States

FDA

To ensure compliance, the _ inspects the facilities and production records of all firms covered by these regulations

(a) requirements for the “Current Good Manufacturing Practice for Finished Pharmaceuticals” and

(b) additional cGMP requirements for biologic products,

(c) medicated articles, and

(d) medical devices

The Code of Federal Regulations (CFR) contains

Active ingredient or active pharmaceutical ingredient (API):

Any component that is intended to furnish pharmacologic activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or function of the body of man or other animals

Batch

: A specific quantity of a drug of uniform specified quality produced according to a single manufacturing order during the same cycle of manufacture

Batchwise control

The use of validated inprocess sampling and testing methods in such a way that results prove that the process has done what it purports to do for the specific batch concerned

Certification

Documented testimony by qualified authorities that a system qualification, calibration, validation, or revalidation has been performed appropriately and that the results are acceptable

Compliance

Determination through inspection of the extent to which a manufacturer is acting in accordance with prescribed regulations, standards, and practices

Component

Any ingredient used in the manufacture of a drug product, including those that may not be present in the finished product

Drug product

A finished form that contains an active drug and inactive ingredients. The term may also include a form that does not contain an active ingredient, such as a placebo.

Inactive ingredient

Any component other than the active ingredients in a drug product

Lot

A batch or any portion of a batch having uniform specified quality and a distinctive identifying lot number

Lot number, control number, or batch number

Any distinctive combination of letters, numbers, or symbols from which the complete history of the manufacture, processing, packaging, holding, and distribution of a batch or lot of a drug product may be determined

Master record

Record containing the formulation, specifications, manufacturing procedures, quality assurance requirements, and labeling of a finished product

Quality assurance

Provision to all concerned the evidence needed to establish confidence that the activities relating to quality are being performed adequately

Quality audit

A documented activity performed in accordance with established procedures on a planned and periodic basis to verify compliance with the procedures to ensure quality

Quality control

The regulatory process through which industry measures actual quality performance, compares it with standards, and acts on the difference

Quality control unit

An organizational element designated by a firm to be responsible for the duties relating to quality control

Quarantine

An area that is marked, designated, or set aside for the holding of incoming components prior to acceptance testing and qualification for use

Representative sample

A sample that accurately portrays the whole

Reprocessing

The activity whereby the finished product

Strength

The concentration of the drug substance per unit dose or volume

Verified

Signed by a second individual or recorded by automated equipment

Validation

Documented evidence that a system (e.g., equipment, software, controls) does what it purports to do

Process validation

Documented evidence that a process (e.g., sterilization) does what it purports to do

Validation protocol

A prospective experimental plan to produce documented evidence that the system has been validated

organization and personnel

The _ section of the regulations deals with the responsibilities of the quality control unit, employees, and consultants.

Organization and Personnel

All personnel engaged in the manufacture, processing, packing, or holding of a drug product, including those in supervisory positions, are required to have the education, training, and/or experience needed to fulfill the assigned responsibility

Organization and Personnel

Appropriate programs of skill development, continuing education and training, and performance evaluations are essential for maintaining quality assurance

buildings and facilities

the regulations in this section include the design, structural features, and functional aspects of

Buildings and Facilities

Each building’s structure, space, design, and placement of equipment must be such to enable thorough cleaning, inspection, and safe and effective use for the designated operations

equipment

Each piece of _ must be of appropriate design and size and suitably located to facilitate operations for its intended use, cleaning, and maintenance.

Equipment

The equipment’s surfaces and parts must not interact with the processes or product’s components so as to alter the purity, strength, or quality

Equipment

Automated equipment and computers used in the processes must be routinely calibrated, maintained, and validated for accuracy.

Control of Components , Containers, and Closures (Written procedures)

describing the receipt, identification, storage, handling, sampling, testing, and approval or rejection of all drug product components, product containers, and closures must be maintained and followed

Controls of Components, Containers, and Closures

Bulk pharmaceutical chemicals, containers, and closures must meet the exact physical and chemical specifications established with the supplier at the time of ordering.

Controls of Components, Containers, and Closures

When product components are received from a supplier, each lot must be logged in with the purchase order number, date of receipt, bill of lading name and vital information of the supplier supplier’s stock or control number and quantity received.

Production and Process Controls

Written procedures are required for production and process controls to ensure that the drug products have the correct identity, strength, quality, and purity.

Production and Process Controls

These procedures, which include the charge-in of all components, use of in-process controls, sample testing, and process and equipment validation, must be followed for quality assurance

Production and Process Controls

Any deviation from the written procedures must be recorded and justified.

Expiration Dating

To assure that a drug product meets applicable standards of identity, strength, quality, and purity at the time of use, it must bear an expiration date determined by appropriate stability testing

Tamper-Evident Packaging

“one having one or more indicators or barriers to entry which, if breached or missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred”.

Tamper- Evident Packaging

The indicators or barriers may involve the immediate drug product container and/or an outer container or carton.

Holding and Distribution

Written procedures must be established and followed for the holding and distribution of product.

Holding and Distribution

Finished pharmaceuticals must be quarantined in storage until released by the quality control unit.

Holding and Distribution

Products must be stored and shipped under conditions that do not affect product quality

Laboratory controls

are requirements for the establishment of and conformance to written specifications, standards, sampling plans, test procedures, and other such mechanisms.