WELCOME TO

Phase 3
Quality
By: Omar Al Agaty
 Manufacturing
process

Research &
• Develop the product formula, production method & analytical method
Development

Registration • Responsible for product file preparation and registration to authorities

(MOH/EDA)

Validation • Validate methods, processes & equipment to ensure sustainable results of

activities)

Planning • Plan for Procurement, storage & production

 Manufacturing
process

Production • Responsible for Products production as per plan and needs

Quality • Review and inspect the system, process and products to ensure Compliance

Warehouse • Responsible to control the inventory (Quantity & Quality)

Commercial quality • Review and audit the product distribution process and conditions till end user
 Manufacturing
process

Complaint handling • Handle complaints and take actions to solve and prevent reoccurrence
 Research and
development R&D

• Responsibilities :-
1- Formulation stage.
(Active pharmaceutical ingredients – excipients - packaging)

2- Development of production process.

(Dispensing – Mixing – Granulation – Compression – Coating – Packaging)

3- Development of analytical method.

 Registration process

1- Product Composition
2- Specification of Raw materials
Some of documents you need 3- MOA (method of analysis)
to register the product:- 4- Validation protocol for method of analysis
5- Master file for Production process
6- Stability studies files
 Validation & Qualification
processes

METHOD VALIDATION
PROCESS VALIDATION
QA
1- IS IT SUCCESSFUL WHEN WE 1- IS THE ANALYTICAL METHOD
MOVE FROM PILOT TO SUITABLE FOR THE PRODUCT ?
PRODUCTION BATCH? 2-IS IT GIVE THE ACCURATE
2- IS IT THE SAME EVERY RESULTS EVERY TIME WE USE IT ?
PRODUCTION CYCLE? FOR EXAMPLE :- IS THE
FOR EXAMPLE : ANALYTICAL METHOD CAN
-MIXING THE SAME DIFFERENTIATE BETWEEN
-COMPRESSION THE DIFFERENT APIS ?
SAMECOATING THE SAME?
 Validation & Qualification
processes

EQUIPMENT
QUALIFICATION

1-IS THE EQUIPMENT GIVE THE

SAME PERFORMANCE EVERY
TIME WE USE IT?
2- WHAT SHOULD WE TEST IN
EQUIPMENT TO ENSURE ITS
PERFORMANCE ?
FOR EXAMPLE :-MIXER
QUALIFICATION, HPLC
QUALIFICATION ?
 Planning (Procurement,
Supply chain)

Raw material Finished product

 Planning Job description

1- Determine the size of production according to market survey from

(sales and business department, …..).
2- Monitor all already present quantities of Raw materials (with
warehouse)
3- Determine all needed Raw materials required for production (with
Supply chain, Purchasing) 
4- Follow up all updates for receiving any materials .
 Production process

Packing Process
Making Process

-Dispensing -Primary packing

-Mixing
-Granulation -Secondary packing
-Compression
-Coating -Tertiary packing
 Quality in product
manufacturing

• Role of quality departments :

• Ensure that the processes of manufacturing and production produce a product complying with the
internal and external standards.
• In general :
- Quality assurance (QA) works to monitor the process.
- Quality control (QC) works to monitor the product.
 Rules of QA Rules of QC

1. IN PROCESS CONTROL 1.RAW MATERIALS (RM)

2. VALIDATION & ANALYSIS.
QUALIFICATION 2. FINISHED PRODUCT
3. TRAINING ANALYSIS.

4. DOCUMENTATION 3. MICROBIOLOGY
ANALYSIS
5. INTERNAL AUDIT
4. STABILITY STUDIES
6. CHANGE & RISK
5. ANALYTICAL METHOD
MANAGEMENT
VALIDATION
 WAREHOUSE

• Stock control.
• prevention of stock damage and
apply GSP(good storage practices)
 External Stages affect product quality
or safety
Storage (warehouse-
Shipment
pharmacy)
 Types of drug complaint

1-Quality complaint 2-Safety complaint

Always related to any physical

changes observed by customer :- Pharmacovigilance (PV) is the
-Deformation of tablets science and activities relating to the
-softening of capsules detection, assessment,
-dusty powders cover capsule shells understanding and prevention of
-separation of emulsions layers adverse effects or any other
-changing of syrup color etc… medicine/vaccine related problem
HPLC AND
GC
HPLC
 HPLC :
(High Performance Liquid Chromatography)

High Pressure Liquid Chromatography

High Price Liquid Chromatography
High Speed Liquid Chromatography

USES ? FIELDS ??? TYPE OF SAMPLES??

separate, identify, and quantify components in liquid samples.
It is applied to various industries and fields, such as pharma and biopharma,
environmental, food , medicine and biology
before HPLC :

Conventional column
chromatography
 Conventional column
HPLC column
chromatography

-Stationary phase: -Stationary phase: 3-5 µm particle

50 µm particle
-Mobile Phase: Driven by high pressure
from
- Mobile Phase: Driven by graphity Low pump High Resolution
resolution
(Observe the narrowing of bands due to
(Observe the broadening of and tailing of bands High resoultion as a result of high surface
due to low resoultion as a result of low surface area due to small particle size)
-Separated compounds are monitored by
area due to large particle size)
means of detector to produce a
-Separated compounds are monitored visibly or chromatogram
under UV
 1. Solvent reservoir: contain the Mobile Phase.
2. Pump: mix the mobile phase with certain ratio and then forces it through the chromatographic column.
3. Injector: introduce the Sample in the course of the mobile phase to be loaded on the column
4. Column: packed with the solid Stationary Phase.
5. Detector: detectes the eluted components and trace a chromatogram for it
2

5
 Solvent Reservoir: bottle of glass.
A channel is transferring the liquid to the degasser before the
pump.
The extremity of the connection tube is supplied with filter
(remove particles which may block the chromatographic
columns and connecting tubes).
Four solvents (A,B,C,D) are connected to the pump heads (4).
Pumps are able of mixing 2-4 solvents to 100% composition.
HPLC solvents are of high purity (HPLC grade) not analytical,
- gives no additional peaks in the
chromatogram

the solutes must be uncharged, so no tailing in

chromatographic peaks occur.

For acidic analytes, make the pH of Mo. (i.e., more acidic).

For basic analytes, pH of Mo.Ph. is (i.e., more basic)
Injector:
manual injector Autosampler

-Up to 100 sample/batch programmed by

-Single injection by analyst each time analyst
-Cheap but time consuming -Expensive but saves time. Conveneient for
-Convenient for Research or small labs
large analytical labs
 Types of stationary phases
eversed phase (RP)
Normal phase (NP) (For separation of nonpolar to modeately polar
(For separation of polar compounds) compounds)

-Polar stationary phase: Silica particles -Nonpolar bonded phase to stationary phase

-mo.ph polar: water

-Non polar mobile phase: hexane, chloroform

-Separation force: Adsorption -Mainly partition and hydrophobic interaction

-Order of elution: least polar to more polar -Order of elution: most polar to least polar
 Types of HPLC columns
-analytical .... Used for analysis (quantification)
-preparative ....Used in isolation of constituents of components
-capillary ....Nanoliter samples
-Chiral columns: for separation of enantiomers, e.g. Quinine and quinidine
-Guard column:to gaurd the chromatographic column against impurities
fraction
collector

Larger
column
 Detectors of HPLC:
1) Visible/Ultraviolet absorption detector (UV/Vis)
Advantages: Cheap and simple.
Disadvantages: limited to compounds have UV/Vis light absorbance.
- Analysis is performed at one wavelength. (e.g., analysis of
mixture of 2 compounds one at 254 nm and other 450 nm, need 2 analytical
runs)
2) Photodiode Array detector (PDA)
Instead of focusing a single wavelength on the flow cell. The full
spectrum of light is focused on the flow cell.
Advantages:
1. Give the UV spectra of the eluted peaks, so help in identification of the
compounds.
2. Mixture of components having different wavelengths can be determined in a
single analytical run.
Disadvantages: 1-Limited to compounds having UV/Vis light absorbance.
2- More expensive than UV/Vis detector.

3) Fluorescence detector:
Detects compounds which fluoresce, e.g., quinine or ergot alkaloids.
-More sensitive than PDA or UV/Vis detectors.
- limited applications
4) Refractive index detector (RI)
Advantages: A universal detector in HPLC.
Can be used in analysis of sugars, terpenoids, surfactants.
Disadvatge: Low sensitivity.

5) Infrared detector (IR)

Give information about functional. ( identification )
Disadvatge: Low sensitivity.

6. Hyphenated (coupled technique) LC-MS

A poweful tool in analysis of natural products.
Help in identification of the eluted compounds.
It is considered as universal detector
Advantages of gradient elution
over isocratic:

1. Elution can be done in shorter

time.
2. Reduce tailing, improve
resolution.
3. Very helpful in analysis of
herbal extracts
 best chromatogram ?
1) retention factor (K´):
t0= dead time of the column
tR= retention time of the peak.
Ideal range: 10>K`>2
(means the peak eluted neither
too late nor too early.

2) Selectivity
3) Resolution
GC ✓It is a chromatographic technique where the mobile phase is gas.
✓It is used mainly for analysis of volatile compounds or compounds which can be
volatilized intact (without decomopsition). Samples could be (gases, liquids or solids).
 Gas cylinder: containing high purity gas (99.999% pure).
Most commonly used gas
is Helium because of
1) its chemical inertness (do not react with sample components ,
2) safety (not explosive).

Other common gases are Nitrogen, Argon and Carbon dioxide.

Selection of carrier gas may depend on the column or the detector
✓Gas cylinder is connecetd to pressure gauge (reads the pressure)
✓Flow controller (adjust the flow rate of the gas)and pressure gauge
✓Injector chamber consist of a glass liner which is heated at high
Temperature (220-270°C) to ensure flash vaporization of the sample

types of columns :
Packed column Capillary column

1-5 m length 5-100 m,

(lower efficiency) (higher efficiency)

Separation in gas chromatography depends on:

1. Boiling point of the solutes where low BP compounds elute first.

2. Interaction between the sample components and the stationary phase.

N.B. In GC, mobile phase plays no role in separation, there is no affinity
competition between St.Ph. and Mo.Ph. For solutes, hence, the name: (Carrier gas)
Sample preparation and introduction

1. Solid samples can be extracted with dichloromethane (DCM) which should dissolve
volatiles only. DCM is a preferable solvent in GC because of its volatility, inertness and
relative high purity.

2. Liquid samples, e.g., volatile oil is mixed DCM.

3. Gases: a sample of the gas is withdrawn by Gas tight syringe.

 Kovat index

Identify these peaks by

referring either to Adams
Book for identification of
essential oils
Herbal Quality Control
By: Ashraqt Eslam
 Herbal drugs
• plants or plant parts that have been converted into phyto-pharmaceuticals
by means of simple processes such as harvesting, drying & storage..

• 80% of worldwide population depend on herbal remides!

 Herbal Quality Control

• In general, QC is based on 3 basic concepts :

- Identity
- Purity
- Assay (content)
WHO monograph
 Identity

• It can be achieved by

Macroscopic Examination Microscopic Examination

AND
shape, size, colour, surface is indispensable for the identification of
characteristics, texture, fracture broken or powdered materials; the
characteristics and appearance of the specimen may have to be treated with
cut surface. chemical reagents.
 Identity

• An examination by microscopy ALONE cannot always provide

complete identification.

• Incorrect botanical quality with respect to the labeling can be a

problem
 Purity

• Closely linked with the safe use of drugs.

• Deals with factors such as ash values, contaminants & heavy
metals, microbial contamination, aflatoxins, radioactivity &
pesticide residues.
• Analytical techniques such as TLC, HPLC & GC can be employed.
 Determination of Heavy
Metals

• Heavy metals such as mercury, lead, copper, The amount present

is estimated by
cadmium, and arsenic can be attributed to comparison with a
environmental pollution. standard

• The main methods commonly used are :

 Determination of
Pesticide Residues

• Method of Detection :
- Gas liquid chromatography (GLC)
- (TLC)
- (GC/MS)

• The procedures and limits for pesticide residues have

been published by WHO
 Determination of
Radioactive
contamination

• There are many sources of ionization radiation, including radionuclides,

naturally occurring in the ground and atmosphere

• The radionuclides were determined by Special spectrometry techniques.

 Determination of Ash
Value

• Total ash is the total weight of the plant material after complete ignition at
temperature of 450°C.

• Total ash is useful in detecting the crude drugs that are mixed with mineral
substances like sand, soil, calcium oxalate, chalk powder. (carbonate,
phosphates, silicates)
.
 Determination of Ash
Value

•  Acid insoluble ash is the residue after extracting the totalash with dil.
HCl. It is indicative of earthy matter (silicate).

•  High acid insoluble ash value indicates contamination ,substitution,

adulteration or carelessness in the preparation of drug

.
 Determination of
Microbial Contaminants

•  Herbal drugs normally carry bacteria and

molds, often originating in the soil.

•  Poor methods of harvesting, cleaning,

drying, handling, and storage may also cause
additional contamination, as may be the case
with Escherichia coli or Salmonella spp.

.
 Determination of
Aflatoxins

• Aflatoxins are natural occurring mycotoxins that

are produced by some aspergillus sp.
• They are carcinogenic substances that are
metabolized by liver to reactive epoxides.
• Aflatoxins can be detected by
o HPLC
o TLC
•  The herbal drug must be free from aflatoxin
 Assay

• The most difficult area of quality control to perform,

since in many herbal drugs the active ingredient is
unknown.

• Some markers can be used.

• In cases where no A.I. can be defined for a herbal

drug, the percentage extractable matter with a solvent
may be used as a form of assay.
Adulteration
 Adulteration

Adulteration in general is the debasement of any

substance or article –drug.
Adulteration whether intended or accidental arise from
various conditions.
 INTRODUCTION TO

Food Quality control

By: Nour Madany
Food Analysis
 Food Analysis

Proximate analysis of major component, Minor

nutrients, trace components & contaminants

"Instrumental analysis"
Food Analysis
What is Food QC?
 Food QC

Testing products to ascertain whether they meet required food safety regulations
and customer requirements.
The purpose?
The purpose

-protect customers from dangers & make sure they get the
quality of the food they pay for.
-To prevent cheating by suppliers.
-To make sure the laws operating in the country are complied
with.
The purpose

safety

Value = money
The purpose

complied with laws

prevent cheating
general specs?
general specs
 Food QC
Appearance Attributes Nutritional
content

Texture Flavour
Appearanc
e
Appearance

bleaching
Textures
 Texture

loss of solubility

loss of water holding capacity

sooftening
Flavour
Flavour

Rancidity
Nutritional content
nutritional content

vitamin
mineral
Protein
Lipid
 Evaluation

Sensory
Chemical

Microbial
 Sensory Evaluation

groups of consumers are used

Expensive & time consuming

Chemical Evaluation
 Chemical Evaluation

• Disinfection Control via Reflectometry and Spectroscopy

• Ingredient Determination such as Salt, Vitamin C, and Calcium by Volumetric Titration
• Water Content Determination by Karl Fischer (KF) Titration
• Trace Element Analysis by Atomic Absorption Spectroscopy (AAS)
• Metal Content Determination by Inductively Coupled Plasma (ICP)
• Planar Pesticide Extraction with the QuEChERS Solid Phase Extraction Sample Preparation Method
• Preparing Food Samples for Direct Instrumental Analysis with Solid Phase Microextraction (SPME)
• Toxin and Pesticide Screening by HPLC and UHPLC (MS-detection)
• Titration
• Determination of Fatty Acid Methyl Esters (FAME) by Gas Chromatography (GC)
• Ingredient Determination of Carbohydrates, Sugars, Lipids, Proteins via Enzymatic Analysis
Water content
Water content

Moisture of food can be determined by various methods, the most

common method is KF (karl fischer)
Karl Fischer
(KF)

Karl Fischer titration is a widespread method used in quality and in-

process control, production, research, and development to determine
the amount of water in solid, liquid, or gas samples.
WHY?
??
Water content

Water can adversely affect quality, stability, and other physical and
chemical properties of raw materials, intermediates, and finished
goods.
Toxin & pesticide screening?
HPLC AND
UPLC
Determination of Fatty Acid
Methyl Esters (FAME) ?
By
GC
NOT
E
Sample preparation for direct
instrumental analysis is by
(SPME)
Microbial Evaluation
Food Microbiology
Food microbiology

Ensuring your food products are safe from microbiological

contaminants is one of the most important steps you can take before
sending them out to market. In fact, it’s often a legislative requirement
around the world at all stages of development.
tests
• Aerobic Plate Count
• Anaerobic Plate Count
• Coliforms
• Lactic Acid Bacteria
• E.coli
• Enterobacteriacea
• Lactobacilli
• Yeast
• Mold
 Culture Media
Immunoassay
PCR s
Immunoassays?
?
Immunoassay
s
Culture Media??
Culture Media
PCR??