QUALITY CONTROL Flashcards
COMBINATION OF ATTRIBUTES which when compared to a standard, serves as a BASIS for measuring the uniformity of a product and determines its degree of acceptability.
QUALITY
as applied to a drug product has been defined as the SUM OF ALL FACTORS which contribute directly or indirectly to the safety, effectiveness, and reliability of the product.
QUALITY
3 MAJOR ELEMENTS considered in quality
FUNCTIONAL
AESTHETIC
TECHNOLOGICAL
– the product meets CONSUMER’S SPECS in point of use. (SAFE & EFFECTIVE as to therapeutic action).
FUNCTIONAL ELEMENT
– the product possesses an ATTRACTIVE DESIGN
AESTHETIC ELEMENT
– the product CAN WITHSTAND SURROUNDING CONDITIONS
TECHNOLOGICAL PROPERTIES
– As the SOLE CRITERION for quality, the product should be WITHIN ITS PRESCRIBE LIMITS OR SEPCIFICATIONS.
CONFORMANCE
– it takes into consideration the DESIGN OR PURPOSE for which the product is made
FITNESS FOR USE
– it is the PROBABILITY that the product WILL PERFORM ITS INTENDED FUNCTION or
mission in the specified environment for a prescribed length of time. Thus, a quality product SHOULD BE EFFECTIVE DURING THE VALIDITY OF ITS LIFE.
RELIABILITY
– a quality product should have MINIMAL OR NO DEFECTS that will result to a high degree of acceptable units produced.
YIELD
– achieving CUSTOMER ACCEPTANCE as a primary objective requires the product to be considered safe, pure and effective. Quality generates REPEATED SALES because the product meets the patient’s needs.
CUSTOMER SATISFACTION
tool which gives the ASSURANCE that a product CONFORMS TO STANDARDS AND SPECIFICATIONS through a system of inspection, analysis and action
QUALITY CONTROL
the activity of providing to all concerned, the EVIDENCE NEEDED TO ESTABLISH CONFIDENCE that the activities relating to quality are being PERFORMED ADEQUATELY.
QUALITY ASSURANCE
is an overall organizational body which aims to GENERATE SUSTAINED CONFIDENCE that the systems of quality control, good manufacturing processes, and environmental control are in place while embracing the principles of Total Quality Management
(TQM).
QUALITY ASSURANCE
MANAGEMENT OBJECTIVES
PLANNIC
LEADING
ORGANIZING
CONTROLLING
one of which involves MONETARY EXPENDITURES AND PROFITS to be gained. It is value-creating and developed to PROTECT COMPANY ASSETS. The company sets a FINANCIAL TARGET or output for the fiscal year and compares current performance against previous and/or projected achievements.
FINANCIAL PLAN
a broad program for DEFINING AND ACHIEVING THE OBJECTIVES of the
organization. It is the organization’s RESPONSE TO ITS ENVIRONMENT over a period of time.
STRATEGY
the design established to MEET the organizations BROAD GOALS. It involves implementation of both financial and operational plans.
STRATEGIC PLAN
a SCHEME that PROVIDES DETAILS needed to incorporate organizational strategy into DAY-TO-DAY OPERATIONS
OPERATIONAL PLAN
CGMP
CURRENT GOOD MANUFACTURING PRACTICES
– is responsible for the DAY-TO-DAY CONTROL OF QUALITY within the company.
Inspection and laboratory testing as well as documentation are integral elements of its function.
QUALITY CONTROL
REVIEWING BODY
COMMITTEE OF REVISION
FOUR CATEGORIES OF CONTROL FUNCTION
ANALYSIS
MONITOR
RECORD REVIEW AND RELEASE
AUDIT FUNCTION
MONITOR AND AUDIT FUNCTIONS are the major keys to determining compliance to standards within the quality system. Compliance ensures that the company’s strategic plans are being implemented.
QUALITY ASSURANCE
ensures that the company’s strategic plans are being implemented
COMPLIANCE
Components such as raw and packaging materials, pharmaceutical products as well as the processes and the environment where they are produced are evaluated by means of pharmacopeial, in-house or regulatory requirements.
DRUG STANDARS
Standards which consist of specifications and procedures for PHARMACOPEIAL SUBSTANCES and finished products are found in published monographs. Commonly used compendia are the United States Pharmacopeia (USP) and National Formulary (NF), British Pharmacopeia (BP), European Pharmacopeia (EP), Japanese Pharmacopeia (JP), and the Philippine Pharmacopeia (PP). Critical parameters which affect the quality of the substances are found in the monographs. Examples are identity, some physical tests, purity tests, alcohol content and assay
PHARMACOPEIAL STANDARDS
USP/NF
UNITED STATES PHARMACOPEIA AND NATIONAL FORMULARY
are UNOFFICIAL STANDARDS generated internally by the
manufacturer or user company for CONTROL PURPOSES. Pharmacopeial requirements allow flexibility of some other criteria which affect the quality of the finished product due to difference in formulation ingredients, manufacturing techniques and equipments. Thus, appearance of finished product, physical characteristics of the dosage form vary from one manufacturer to another. Additional criteria are included as mandatory in-house tests to satisfy the needs of good manufacturing practices. An example would be the need for determination of particle size of a raw material to control variability of suspended materials.
IN-HOUSE STANDARDS
allow FLEXIBILITY of some other criteria which affect the quality of the finished product due to difference in formulation ingredients, manufacturing techniques and equipments.
PHARMACOPEIAL REQUIREMENTS
are those MANDATED BY THE REGULATORY AGENCY such as the Food and Drug Administration (FDA). These are required for registration purposes and regulatory compliance. An example is the comparative and multipoint dissolution test for products. When the dissolution profile of a generic drug in several dissolution media is similar to the innovator drug, the generic drug is considered by the FDA to have the same bioavailability as the innovator drug.
Other regulatory standards are those issued by the World Health Organization
(WHO), the United States Food and Drug Administration (US FDA) and the
International Conference on Harmonization (ICH).
REGULATORY STANDARDS
FDA
FOOD AND DRUG ADMINISTRATION
WHO
WORLD HEALTH ORGANIZATION
US FDA
UNITED STATES FOOD AND DRUG ADMINISTRATION
ICH
INTERNATIONAL CONFERENCE ON HARMONIZATION
Quality characteristics are interpreted by
DESCRIPTIVE WORDS AND MEASUREMENTS
a BASIS for ACCEPTING or REJECTING a product
STANDARDS AND SPECIFICATIONS
This is CONCISE AND PRECISE STATEMENT of the ingredients that comprise the product, together with the percentage and/or weight of each.
FORMULA
This should ENUMERATE the characteristics of all the materials that go into the product and the permissible RANGE OF PURITY of each ingredient. Deviation beyond this range may be expected to cause failure of the product to function as planned or, at least, result in an undesirable lack of uniformity.
RAW MATERIAL SPECIFICATION
This is the STEP-BY-STEP METHOD on how to go about an activity or job. It must spell out all information and instructions that assure that variations in production from day to day and week to week will be held to within ACCEPTABLE ESTABLISHED RANGES.
STANDARD OPERATING PROCEDURE
This should COVER ALL CHARACTERISTICS that AFFECT THE PROPER PERFORMANCE, purity, safety and stability of the product. Tolerances may be minimum, maximum, or both, depending on the situation.
FINISHED PRODUCT SPECIFICATION
This should be set for EVERYTHING THAT GOES AROUND THE PRODUCT: i.e., bottles, cans, aluminum foil, cellophane, jars, caps, or cap liners, labels, package inserts, cartoons, wrapping paper, and shipping case.
PACKAGING MATERIAL/COMPONENTS
These are procedures which are STANDARDIZED AND OR VALIDATED so that they yield a result of comparable precision, accuracy or specificity and linearity.
TEST METHODS
GMP
GOOD MANUFACTURING PRACTICES
ISO
INTERNATIONAL ORGANIZATION FOR STANDARDIZATION
has developed INDUSTRIAL STANDARDS for worldwide trading or participation to global economy
ISO
WHERE IS ISO
GENEVA, SWITZERLAND
ISO SERIES OF STANDARDS
9000 - 9004
Quality Management and Quality Assurance Standards – GUIDELINES FOR SELECTION AND USE (To determine which standard applies to the specific organization). The focus is how the management system ASSURES QUALITY OF PARTS AND SERVICES a company produces.
ISO 9000
Quality Systems – Model for Quality Assurance in DESIGN/DEVELOPMENT, PRODUCTION, INSTALLATION AND SERVICING (For companies engaged in MANUFACTURING or in the development and delivery of a service).
ISO 9001
Quality Systems – Model for Quality Assurance in PRODUCTION AND INSTALLATION (For companies that perform all functions EXCEPT DESIGN AND DEVELOPMENT of products and services).
ISO 9002
Quality Systems – Model for Quality Assurance in FINAL INSPECTION AND TEST (For NON-MANUFACTURING companies such as distributor or warehousing operations).
ISO 9003
Quality Management and Quality System Element – Guideline (To help interpret ISO 9001, ISO 9002, and ISO 9003).
ISO 9004
local accredited assessor for certification
CERTIFICATION INTERNATION PHILIPPINES
“Laboratory control shall include the establishment of scientifically sound and appropriate specifications, standards, and test procedures to assure that components, drug preparations in the course of processing, and finished products conform to appropriate standards of identity, strength quality and purity”.
ADMINISTRATIVE ORDER NO. 220 s. 1974
To perform the necessary tests, the Food and Drug Administration issued the minimum requirements for a quality control facility of drug manufacturers as an addendum to Administrative Order No. ____ s. _____.
Administrative Order No. 56 s. 1989
applied to ALL ANIMAL STUDIES, such as toxicology, pharmacology and animal pharmacokinetics (toxicokinetics)
GLP / GOOD LABORATORY PRACTICE
Studies involving HUMANS
GOOD CLINICAL PRACTICE
Is intended to promote the QUALITY AND VALIDITY of test data. It is a managerial concept covering the organizational process and the conditions under which laboratory studies are planned, performed, monitored, recorded and reported (Singer and Upton, 1993).
GLP
OECD
Organization for Economic Cooperation and Development
The Organization for Economic Cooperation and Development (OECD) Principles of GLP, was established in
1978
The Organization for Economic Cooperation and Development (OECD) Principles of GLP, was established in 1978 under the Special Programme on the
CONTROL OF CHEMICALS
should be applied to testing of chemicals to obtain data on their properties and/or their safety with respect to human health or the environment.
GLP
The laboratory practice regulations by the ________
prescribed good laboratory practices for conducting non-clinical laboratory studies that support or are INTENDED TO SUPPORT APPLICATIONS FOR RESEARCH OR MARKETING PERMITS for products regulated by the FDA, including food and other additives, animal food additives, human and animal drugs, medical devices for human use, biological products, and electronic products. Compliance is intended to assure quality and integrity of the safety data filed to the regulatory agency.
US FDA
_______ means any in vivo or in vitro experiment in which a test article is studied prospectively in a test system under laboratory conditions to determine its safety. It includes a broad range of studies to obtain toxicology data
NON-CLINICAL LABORATORY STUDY
_____ is EXTREMELY CRITICAL in a quality control laboratory since it records a wide range of administrative and operational information such as standard operating procedures, test methods, analytical data, preventive maintenance for instruments and the prevailing laboratory or environmental conditions a time of test.
DOCUMENTATION
is an UNDESRIABLE CHARACTERISTICS of a product
DEFECTS
It is defined as a FAILUREto conform to specification.
DEFECTS
A unit of a product which contains ONE OR MORE DEFECTS.
DEFECTIVE
– a defect which CAN BE MEASURED DIRECTLY by instruments giving dimensions of length, weight, height, thickness, concentration, volume, viscosity pH or size particles.
VARIABLE DEFECT
– a defect which CANNOT BE MEASURED DIRECTLY by instruments. It shows mainly the conformance or nonconformance of the material to specifications.
ATTRIBUTE DEFECTS
– a defect which may ENDANGER LIFE OR PROPERTY and may render the product NON-FUNCTIONAL.
CRITICAL DEFECT
– a defect which may AFFECT THE FUNCTION of the object and therefore may render the product USELESS.
MAJOR DEFECT
– a defect which does not endanger life or property nor will it affect the function but remains a defect since it is OUTSIDE THE PRESCRIBED LIMITS.
MINOR DEFECT
– a defect that is VISIBLE
OCULAR DEFECT
– a defect which is NOT SEEN although present
INTERNAL DEFECT
– a defect in FUNCTION
PERFORMANCE DEFECT
SOURCES OF VARIATION OF DEFECTS
MATERIALS
MACHINES
METHODS
MEN
ESSENTIAL ELEMENTS OF QUALITY
MATERIALS
MACHINES
METHODS
MEN
MONEY
established & implemented by Pharmaceutical Manufacturers Association in 1967
General principles of Total Quality Control in the drug Industry
established & implemented by Food & Drug Administration.
Current Good Manufacturing Practices CGMP
2 FACTORS RESPONSIBLE FOR ASSURING SAFETY & THERAPEUTIC EFFICACY OF DRUGS
INTERNAL & EXTERNAL FACTOR
This section of the regulation deals with the RESPONSIBILITIES of the quality control unit, employees, and consultants.
ORGANIZATION & PERSONEL
The regulations in this section include the design, structural features, and functional aspects of buildings and facilities.
BUILDINGS & FACILITIES
The equipment’s surfaces and parts must not interact with the processes or product’s components so as to alter the ______, ______, or ______.
PURITY, STRENGTH, QUALITY
– the PARTIAL SUBSTITUTIONS of substance to another W/O ACKNOWLEDGEMENT
ADULTERATION
– impairment of the condition or quality of the drug.
DETERIORATION
– an INITATION OR REPLICA markedly close or faithful to an original.
COUNTERFEIT
– to brand FALSELY or in a MISLEADING WAY (drug containers).
MISBRANDING
will serve to improve productivity & customer satisfaction.
TOTAL QUALITY MANAGEMENT
emphasis is directed toward defect PREVENTION rather than defect detection.
TQM
the quality function is part of a team composed of research, production, marketing/sales & customer service
TQM
can be looked upon as a combined team effort to develop, produce, market, distribute & control products that are safe & will remain effective for the time they remain in the
marketplace.
TQM
this program will assure the professional dispenser & the final customer that each lot of every product conforms to contain specifications & that each unit will fulfill the declaration made in its labeling & has met all the requirements both internal & external of the industry.
TQM
the concept of ______ requires the total commitment of senior level management & supervision of all departments, operators, suppliers & customers
TQM
Distribution departments are responsible for controlling the shipping & handling of products, using inventory control systems based on the
FIRST IN FIRST OUT PRINCIPLE (FIFO)
It relates to the CLOSENESS OF TEST RESULTS to true value, i.e., measure of exactness of analytical method.
ACCURACY
It is expressed as % recovery by the assay of known/added amount of analyte in the linearity range.
ACCURACY
It can also be determined by comparing the results with those obtained using an alternative method which has already been validated.
ACCURACY
It expresses a DEGREE OF AGREEMENT among individual test results when procedure/method is applied to homogenous sample.
PRECISION
It is usually expressed as SD/RSD.
It is a measure of DEGREE OF REPEATABILITY OR REPRODUCIBILITY under normal conditions.
PRECISION
Precision of the method when repeated by the same analyst, same test method and under same set of laboratory conditions (reagent, equipment, etc.) within short interval of time, THE ONLY DIFFERENCE BEING THE SAMPLE.
REPEATABILITY
– When the subject method is
carried out by different analyst in different laboratories, using different equipments, reagents, and laboratory settings and on different days-variability of analytical results as function of analyst, day-to-day, laboratory to laboratory,
equipment to equipment, etc. using the sample from same homogenous batch.
REPRODUCIBILITY
Within the SAME LABORATORY BUT DIFFERENT DAYS, analysts, equipments and
reagents.
INTERMEDIATE PRECISION
Ability of the method to measure ACCURATELY AND SPECIFICALLY the analyte of interest in presence of matrix and other components likely to be present in the sample matrix and impurities, degradation products and other related substance.
SELECTIVITY / SPECIFICITY
Ability of the method to ELICIT TEST RESULTS that are directly proportional to the concentration of analyte.
LINEARITY
LOWEST AND HIGHEST LEVEL of analyte but the method can determine with reasonable accuracy and precision.
RANGE
LOWEST CONCENTRATION OF THE ANALYTE in the sample that the method can detect but not necessarily quantify under the stated experimental conditions simply indicates that the sample is below or above certain level.
LIMIT OF DETECTION
Degree of reproducibility of test results obtained by analyzing the SAME SAMPLE UNDER VARIETY OF NORMAL TEST CONDITIONS such as different analyst, instruments, days, reagents, columns, and TLC plates.
RUGGEDNESS
Is the measure of the CAPACITY of the analytical method to REMAIN UNAFFECTED by small but deliberate variations in procedure.
ROBUSTNESS
Capacity of the test procedure to RECORD SMALL VARIATIONS in concentrations.
SENSITIVITY
AVERAGE WEIGHT FORMULA
TOTAL WEIGHT / NUMBER OF SAMPLE
ilan ang need na ikeep na product
2 labeled containers
gano katagal pwede ikeep ung 2 labeled containers
2 years after distribution / expiry date
how to determine the expiry date
manuf date + shelf life
DR
drug registration number
a dehydrating agent
silica gel
- developed by CIBA, a swiss pharmaceutical company in the early 1950s
- advertised as sedative
- allows user to undergo a deep sleep in the absence of hangover
- reduced risk of developing drug dependency
- was told to be safe for pregnant women; anti-emetic; turns out to result into congenital deformity
THALIDOMIDE
a congenital deformity that is a result of thalidomide in pregnant women
PHOCOEMELIA
he avoided the tragedy of thalidomide by not allowing the drug to enter the US
FRANCIS KELSEY
accdng to US FDA LAB PRACTICE REGULATIONS, hanggang ilang tries lang pwede sa animal trial
5 trials max
verification by data & analysis
VALIDATION
one that has been shown by appropriate scientific means to be uniform
VALIDATED PRODUCT
VALIDATION STEPS
- mean
- range
- average deviation (d)
- RAD
- standard deviation (s)
- RSD
- true value
FORMULA:
mean
summation of x / number of samples
FORMULA:
range
highest value - lowest value
FORMULA:
average deviation (d)
summation of x - xbar / number of samples
FORMULA:
RAD
average dev / mean x 1000
FORMULA:
standard deviation (s)
square root of summation of x - xbar squared / number of sample - 1
FORMULA:
RSD
standard dev / mean x 100
FORMULA:
true value
mean +- standard dev
apparatus
VITRO
living things
VIVO
