QUALITY ASSURANCE

process approach

done before starting a project

process documentation, establishing standard, audits

QUALITY CONTROL

product based approach

deliverables are in good quality

begins once the product has been manufactured

note:

Both Quality assurance and Quality Control are largely interdependent

Both Quality Control and Quality Assurance

- because of strong interdependence, it becomes difficult to pinpoint the difference

- very thin line that separates the 2

- in some organizations, one department performs the functions of both

Pharmaceutical and Cosmetic manufacturing:

Comply CGMP (AO# 220 s. 1974)

Quality

Is everybodys business

Quality Control

A tool which gives assurance that product conforms to standards and specifications

Success as an Analyst

manipulative skill by experience

follow directions

knowledge of the theory

skill of technique, patience, neatness and accuracy

Accuracy and Honesty

the operator is the only person who is familiar with the entire history of the analysis

at least two determinations are required

the results should agree closely

Documentation/Notebook

include date

object or title

experimental data

reactions

calculations\results

remarks

Economy of Time

clean apparatus immediately after using

label all solutions, filtrates and precipitate

keep 2 or more operations going at one time

utilize all time between operations in making calculations and writing up experiments

Reagents

must be pure

conform to USP and NF

Sampling

secure a representative samples

sampled from different parts, top to bottom

Standards and Specifications

basis for accepting or rejecting a product

DEFECTS

undesirable characteristics of a product

failure to conform to specs

1. according to measurability

a. attribute defect

cannot be measured by instrument

odor, cleanliness

b. variable defect

measured by instruments

pH, weight, thickness, conc.

2. according to seriousness or gravity

a. critical defect

endanger life or property

may render product non functional

disintegration time

b. major defect

may render product useless

cracked bottle

c. minor defect

not endanger life nor affect function

color label

3. according to nature

a. ocular defect

visible (foreign particulate)

b. internal defect

not seen

subpotent

c. performance defect

a defect in function

suppository does not melt in body temp

SOURCES AND CONTROL OF QUALITY VARIATION

Materials

Machines

Methods

Men

A. MATERIAL INSPECTION SECTION

examine raw materials received

conduct physical test packaging materials

examination on the quality of inventories

B. ANALYTICAL LABORATORY

perform chemical and physical analysis

C. BIOLOGICAL TESTING LABORATORY

perform microbiological, pharmacological, sterility, toxicity tests

conduct environmental monitoring

D. ANALYTICAL DEVELOPMENT

research development

validate procedures

develop new assays

develop and improve final product

E. QUALITY COORDINATION OFFICE

maintain records

investigate complaints

maintain and develop SOP

A. raw materials

1. Reception - RTR

2. quarantine

- hold sticker

- samples submitted to lab

- no stickers of different disposition

3. rejected

4. approved

B. stickers

to avoid mixups

colors:

yellow = quarantine/ hold/ pending

green = approved/ pass

red = rejected/ fail

C. printed and packaging materials – direct contact

1. primary packaging components – capsules, bottles, caps

2. secondary – labels, inserts, cartons

D. Reassay dates

the date of retest

Monthly or prior to use – highly unstable

6 months – vitamins, flavors

12 months – dyes

24 months – excipients

BATCH

Means specific amount produced in a unit time or according to single manufacturing order during same cycle of manufacture

LOT

A batch

Any portion of a batch

DISTRIBUTION CONTROL

Certificate ANTIBIOTICS and INSULIN are withheld from distribution until BATCH CERTIFICATE from BFAD is received

Mean

average

Average Deviation (d)

Difference between individual results and the mean, regardless of signs, adding these differences and dividing by the # of determinations

Relative average deviation

Dividing the average deviation by mean and multiplied by 100 as % or 1000 as ppt

Standard Deviation (sd, s)

Preferred measure of precision

Relative Standard Deviation (RSD)

Or coefficient of variation

Dividing the standard deviation by mean and multiply by 100

Range (R)

Largest and smallest values

Ex.

Get the mean, average deviation, relative average deviation, standard deviation (SD) and RSD of the following values:

0.1140

0.1142

0.1152

0.1146

QC CHARTS:

2 types:

1. attribute chart

P chart (control chart for fraction defective)

2. variable chart –

use of actual records of numerical measurement

ex. meter, grams

X and R charts

CONTROL CHARTS consist of:

1. Control solid line – average

2. 2 horizontal parallel lines – indicates limits

UCL (upper control limit): mean + 3 (SD)

above center line

LCL (lower control limit): mean - 3 (SD)

below center line

VALIDATION

Verification

A. Process Validation

- temperature, blending time, dissolution (rpm)

B. Assay Validation

- estimate of assay accuracy and precision

C. validation of equipment – calibration

D. validation of existing products – potency, content uniformity

E. cleaning validation – avoid contamination

F. post validation – if there is change in formulation, analytical methods

CLEANING SOLUTIONS

Sodium dichromate in sulfuric acid - best

Chromic acid

soln. of trisodium phosphate

Synthetic detergent

CALCULATION OF RESULTS AND ERRORS

Source and Nature of Errors

generally, results that agree closely when obtained by 2 different methods of analysis are a good indication of the reliability of the methods

2 types errors:

1. Indeterminate errors

slight variation in a series of observations by same observer

result from causes difficult to detect such as differences in the judgment and skill of the analyst

intangible and their elimination is impossible

Random or accidental error

2. Determinate errors

Also called systematic error

recur in constant manner/error

arise from causes such as:

a. personal errors (inability to judge color change)

b. incorrect sampling, contamination, error of method

c. apparatus errors ( inaccurate calibration)

errors are detectable and so may be eliminated

Precision or reproducibility – agreement among repeated measurements

Accuracy – closeness of measurement to true value

Accuracy

denote the agreement of results

expressed in term of errors

the difference between the mean and the true value is known as the ABSOLUTE ERROR

the RELATIVE ERROR is found by dividing the absolute error by the true value and multiplied by 100

Precision

a measure of reproducibility of data within a series pf results

results within a series which agree closely with one another are said to be precise

precise results are not necessarily accurate

Constant Weight

2 consecutive weighings do not differ by more than 0.5 mg/g of substance

if 2 weights agree within 0.2 mg

Analytical Balance

double pan

single pan

top

analytical

Weights

substance to be accurately weighed for an assay, error is limited to 0.1% or less

a quantity of 500 mg is to be weighed to the nearest 0.5 mg

Dessicators

Vessel rendered airtight

Maintain dry atmosphere

Has dehydrating agent/ dessicant (silica gel, calcium chloride)