Lesson 3 - CGMP

Current Good Manufacturing Practice (cGMP)

• Regulations are established by the Food and Drug Administration (FDA) to esure that minimum standards are met for drug product quality

• apply to foreign and domestic suppliers and manufacturers whose bulk components and finished pharmacuetical products are imported, distributed, or sold

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 quality 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 in process sampling and testing methods in such a way that results prove that the process has done what it purports to do for 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

• 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 placebo

Lot

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

• can also refer to a specific quantity of material or product that is produced, processed, or packaged together

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 the 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 the quality control

Quarantine

• an area that is marketed, 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

• this activity whereby the finished product or any of its components is recycled through all or part of the manufacturing process

Verified

• signed by a second individual or recorded by automated equipment

Strength

• the concentration of the drug substance per unit dose or volume

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. sterilzation) 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

• Deals with the responsibilities of the quality control unit, employees, and consultants

Quality Control Unit

• have the authority and responsibility for all functions that may affect product quality

• this includes accepting or rejecting product components, product specifications, finished products, packaging, and labeling.

Design and Construction features

• 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

• must be of appropriate design and size and suitably located to facilitate operations for its intended use, cleaning, and maintenance

Rejected

• components, drug product containers, and closures are identified and controlled under a quaratine system to prevent their use in manufacturing and processing operations

Written procedures

• are required for production and process controls

• ensure that the drug products have the correct identity, strength, quality, and purity

Performed by production personnel and Performed by the control laboratory personnel

Two general types of in-process controls:

Performed by production personnel

In-process control type:

• at the time of operation to ensure that the machinery is producing output within preestablished control limits (e.g. tablet size, hardness)

Performed by the quality control laboratory personnel

In-process control type:

• to ensure compliance with all the product specifications (e.g. tablet content, dissolution) and batch-to-batch consistency

Labelling

• for each variation in drug product - strength, dosage form, or quantity of contents — must be stored separately with suitable identification

• facilitate product identification

Expiration date and production batch or lot number

Each label must contain:

Tamper-Evident Package

• “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 occured”

Expiration Date

• to ensure that a drug product meets applicable standards of identity, strength, quality, and purity at the time of use

Finished Pharmaceuticals

• must be quarantined in storage until released by the quality control unit

Laboratory Controls

• are requirements for the establishment of written specifications, standards, sampling plans, test procedurs, and other such mechanisms

Reserve samples

• must be maintained for 1 to 3 years after the expiration date of the last lot of the drug product

Production, control, and distribution records

• must be maintained for at least a year following the expiraiton date of a product batch

Returned drug products

• must be identified by lot number and product quality determined through appropriate testing

Phase 3

• under what phase in the clinical trial that all of the regulatory requirements are expected to be met

Process optimization

• the manufacturer must produce a batch of the drug that is at least one-tenth the size of a commerical batch

Medical devices

• follow a path for FDA approval that resembles that for pharmaceuticals

Compounding

• involves the customization of a medication to fulfill the precise requirements outlined by the prescriber when a commercially availble drug doses does not meet those needs