CEE 4: MODULE 6 - QA & QC

Total features or conformance to specification of a product

Quality

A list of detailed requirements with which a product has to conform (test, references of procedures, and acceptance criteria)

Specification

"QUALITY IS EVERYBODY'S BUSINESS" ⭐

TOTAL QUALITY MANAGEMENT (TQM)

Sum total of the organized activities made with the objective of ensuring that products are of quality requires for intended use

QUALITY ASSURANCE

Part of QA which ensures that products are consistently produced & controlled to quality standards appropriate to intended use

Current Good Manufacturing practice

Old cGMP

AO 220s. 1974

Current cGMP

2012-0008 (curre8)

Part of cGMP concerned with sampling, specification, testing, organization, documentation, and release procedures.

Quality Control

"If it is not written, it did not happen"

Documentation

It is the linkage between written records of action taken and the quality operation

Documentation

all the tests to be conducted on a product and raw materials and/or appropriate references containing DETAILS OF PROCEDURE and EXPECTED RESULTS vs ACTUAL RESULTS

Documentation

Regular periodic quality review of all registered drug products to verify consistency of existing processes and to identify improvements

Product Quality Review (PDR)

CAPA (Corrective & Preventive Action)

Product Quality Review (PDR)

Systemic process for the assessment, control, communication, and review of risks to the quality of the product

Quality Risk Management (QRM)

A combination of probabiluty of the occurance of harm and the severity of harm

Risk

An organized unit indepent of production which fulfills both QA and QC

Quality Unit

A set of activities that ensure quality in the process by which the product are developed

Quality Assurance (Manager)

Aims to prevent defects in the process used to make the prodects

Quality Assurance

Process-oriented

Quality Assurance

A set of activities that ensures quality in the products

Quality Control (workers)

Aims identify and correct defects in the finished product

Quality Control

Product-oriented

Quality Control

Testing the quality of bulk ingredients and containers

Raw Materials QC (RMQC)

Testing the quality of intermediate products (e.g. granules prior tablet compression)

In-process Material QC (IPQC)

Testing the final dosage form in it's container

Finished product QC (FPQC)

Written standard published in compendium (USP/BP/Eur/PP) that describes an article. Quality attributes approved by a regulatory body.

Monograph

Step-by-step instruction for doing a particular task or activity

SOP (by QA)

Shows the actual results of all tests conducted to show compliance with standards. Describes the tests conducted on a particular material, along with the acceptable criteria, results, and disposition

Certificate of analysis

Information on potential health effects of exposure and safe working procedures when handling. Properties of a particular hazardous substance or chemical.

MSDS

Process of removal of an appropriate of an appropriate number of items (n) from a population (N) in order to make an inference to the entire population

Sampling

Most common and old military standard sampling

MIL-STD-105E

A military sampling standard by variable

MIL-STD-144

most common and new sampling method

ANSI/ASQ ZI. 4-2008

An easier sampling method often used in exam

Square root system

What is the percentage of inspection that may be allowed for high risk medications

100%

A definite working rule regarding size and frequency of sample and the basis for acceptance and rejection. It requires 3 numbers

Sampling Plan

Graphs on which the quality of product is plotted as manufacturing is actually proceeding

Control Charts

used for proportion or % of defectsives, versatile, and most used. It is used when n is not always constant

p-Chart

used in non-proportion, number of defectives and used when n is always constant.

np-Chart

Used for measurable characteristics: 3 sigma rule

X bar chart (XMEN)

Alerts the operator to closely monitor the process

Warning Limit

Stop the process and do corrective actions

Action limit

Risk of rejecting a true null

alpha risk/type 1 error

a false negative

alpha risk/type 1 error

An inspection/test may indicate that a product or process

alpha risk/type 1 error

A false negative is a:

Beta risk, aka type II error

Accepting a false negative null hypothesis (bad result)

Beta risk, aka type II error

An inspection/test may indicate that a product or process is acceptable when it is actually defective

Beta risk, aka type II error

it harms the company

Beta risk, aka type II error

It can be reduced by increasing sample size or improving the accuracy of the measurement tool

Beta risk, aka type II error

It estimates shelf-life. Evaluated over time in the same container-closure-closure system in which drug product is marketed based on ASEAN Guidelines on stability studies

Stability Studies

temperate climate

Zone I

Subtropical/Mediterranean climate ⭐

Zone II

Hot and Dry climate ⭐

Zone III

Hot and Humid climate ⭐

Zone IVa

Hot and very humid climate ⭐

Zone IVb

A test conducted under normal conditions

Long-term/Real Time stidies

A test that follows zero-order kinetics

long-term/real-time studies

(l00000ng)

Designed to increase rate of chemical degradation by using exaggerated storage conditions

Short-term/accelerated studies

a test that follows first-order kinetics

Short-term/accelerated studies

Elucidates intrinsic stability of drug & identify the likely degradation productions

Stress Testing

Proving & documenting that any process, procedure, or method actually leads to the expected results.

Validation

Proving that premises, systems, or equipment work correctly and actually lead to expected results

Qualification

A continuous type of data

Variable

A whole type of data

Attribute

The quality between supplier 1 and 2 are not the same

Material

some parts of the equipment are not well-maintained

Machine

The working instruction is written in jargon

Method

Overfatigue, lacking PPE

Man

Non conformance to a standard or requirement ⭐

Product Defect

May endanger the life of patient and render the product non-functional

Critical defect

May affect the function of product and render it useless

Major defect

Neither have significant effects on product or life.

e. g. discoloration, labels

Minor defects

A defect measured by instrument

Variable defect

A defect detected by inspection (senses)

Attribute

A defect seen by the naked eye

Ocular defect

A defect that cannot be seen by the naked eye (e.g. Concentration)

Internal Defect

A defect where function is incorrect (MDI, dissol.)

Performance defect

Classify the defect:

The actuator of the MDI is stuck

Major

Classify the defect:

Metal Particles inside a parenteral vial

Critical

Classify the type of defect:

Minor

Classify the defect:

Scratches on the amber bottle surface of an oral syrup

Minor

Removal from the market; either defective/potentially harmful

Product recall

Class of product recall:

Caused death or serious ADR

Class I

Class of product recall:

Causes temporary or medically reversible ADR

Class II

Class of product recall:

It is not likely to cause any serious ADR

Class III

It is the capacity of the drug to remain within specification

Stability

The minimum acceptable potency

90%

It is prevented by reduction of water from preparation

Hydrolysis

it is prevented by an antioxidant

Oxidation

It is prevented by using light containers

Photolysis

A period or time during which a product remains within specification

Shelf-life (t90)

Shelf-life (t90) is estimated using what equation?

Arrhenius equation

The time or date prior to which a product is expected to remain table & after which it must not be used

Expiration Date

Status of materials which are isolated physically while a decision is awaited on their release, rejection or reprocessing

Quarantine

All quarantine materials are labeled with what color?

Yellow color

Materials that conform to the tests are labeled with what color?

Green color

Materials that are rejected are labeled with what color?

Red color

stocks brought first are used first

FIFO

stocks expiring first are used first

FEFO