Unit III

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Subject Name: Quality Assurance Module -III

Subject Code: BP 606T

Objectives of the course

➢ Understand the scope of quality certifications applicable to pharmaceutical industries.

Learning outcomes
➢ Students learnt about the quality assurance and quality control parameters which affects
academics as well as pharmaceutical industry.
➢ Students learnt about the good laboratory practices in association with equipment
documentation, testing facilities operation and records.
Structure of Module -3BP 606T
Learning Material

Quality Control- Quality control test for containers, rubber closures and secondary packing materials.
Good Laboratory Practices- General Provisions, Organization and Personnel, Facilities, Equipment,
Testing Facilities Operation, Test and Control Articles, Protocol for Conduct of a Nonclinical
Laboratory Study, Records and Reports, Disqualification of Testing Facilities.
GOOD
LABORATORY
PRACTICES
GLP: GOOD LABORATORY PRACTICE

GLP is an FDA regulation.


GLP is a formal regulation that was created by the FDA (United states food
and drug administration) in 1978.
What is GLP?

Good Laboratory Practice (GLP) is a quality system concerned


with the organisational process and the conditions under
which non-clinical health and environmental safety studies are
planned, performed, monitored, recorded, archived and reported.
WHY WAS GLP CREATED?

In the early 70’s FDA became aware of cases


of poor laboratory practice all over the
United States.
They discovered a lot fraudulent activities and
a lot of poor lab practices.
Examples of some of these poor lab
practices found were
1. Equipment not been calibrated to
standard form , therefore giving wrong
measurements.
2. Incorrect/inaccurate accounts of the
actual lab study.
3. Inadequate test systems.
Purpose of GLPs:

• GLP is to certify that every step of the


analysis is valid or Not.

• Assure the quality & integrity of data


submitted to FDA in support of the safety
of regulated products.

• GLPs have heavy emphasis on data


recording, record & specimen retention.
Scope of GLP

Principles of GLP apply to all non-clinical health and


environmental safety studies required by regulations
for the purpose of registering or licensing -

Pharmaceuticals
Pesticides
Food and feed additives
Cosmetic products
Veterinary drug products and similar products
Industrial chemicals
Objectives of GLP
True reflection
Ensure Honesty International acceptance
GLP makes sure Promotes
that the data GLP also makes internation
submitted are a sure that not to al
true reflection of indulge in any acceptance
the results that are fraud activity by of tests
obtained during labs
the study.
Protocols of GLP
Ensure sufficient number of qualified personnel, appropriate
facilities, equipment, and materials

Ensure the maintenance of a record of the qualifications, training,


experience.

Proper training of personnel to assigned functions

Job description for each professional and technical individual.

To establish and follow SOP

Quality assurance program with designated personnel


Organisation & Personnel – Study Director’s responsibi
Approval of protocols & the study plan including
amendments

Ensure QA personnel and study personnel are


updated with study plans & SOP

Ensure the follow up of SOPs periodically and


take appropriate corrective action

Archiving Raw data, supporting materials and


final report.
Organisation & Personnel
Principal Investigator’s Responsibilities

Ensures the study is conducted in


accordance with GLP
Study Personnel’s Responsibilities
Recording of all raw data in compliance
with the principles of GLP

Deviations from the instructions to be


reported the PI or SD

Takes health precautions and personal


safety
Quality Assurance Programme
An individual or a group designated
by management to assure studies are
in compliance with GLP Principles
Maintains copies of protocols & SOPs

Inspects each laboratories and man at work –


inspections based-Study
Facility-based inspections
Process- based inspections

Determines any deviation from approved protocol and report to


SD, PI & management

Prepare a statements to be included in final report containing


dates & types of inspection
13
Facilities

Test System Facilities


Sufficient amount of rooms and areas to assure isolation
of test systems

Adequately protected storage area separate from test


systems
Areas available for the diagnosis, treatment and control
of diseases
Archive facilities

Secure storage and retrieval of study plans, raw data, final


reports & specimen to prevent deterioration

Waste Disposal

Appropriate collection, storage & disposal facilities and


decontamination procedures
Apparatus, Materials & Reagents

Apparatus to be
Apparatus, including periodically inspected,
validated computerised cleaned, maintained,
systems should be of and calibrated
appropriate design & according to Standard
adequate capacity Operating Procedures.

Chemicals, reagents
and solutions should Should not
be labelled to indicate interfere adversely
identity, DOE & with the test
storage instructions systems.
5. Test Systems

Physical/ Chemical

Biological
6. Test and Reference Items

• Receipt, handling, sampling and storage


• Characterization.
• Known stability of test and reference items.
• Stability of the test item in its vehicle
(container).
• Samples for analytical purposes for each
batch
7.Standard Operating Procedures (SOP)
1. Test facility should have a written SOP approved by management

2. SOPs should be available wherever applicable e.g.

Test and reference items


reagents and materials Apparatus,
Record keeping, reporting, storage and retrieval
system Test
Quality assurance procedures

3.Any deviations from SOP should be


documented & acknowledged by SD and PI
Performance of The Study
For each study, a written plan –
• Approved by SD, management, sponsor
• Verified for GLP compliance by QAU
• If required, national regulation

Contents of Study Plan

Identification of the study, the test and


reference item
Information - sponsor and the test facility, SD,
PI
Test methods – reference to OECD/other test
guidelines
Issues – justification of selection
Records
Storage & Retention of Records 21

The study plan, raw data, samples of test and


reference items, specimens and the final
report of each study.

Records of all inspections by QAP

Records of qualifications, training, experience


and job descriptions of personnel.

Records and reports of the maintenance and


calibration of apparatus.

Historical files of all SOP.


Definition
Role Of Packaging Material
Types Of Packaging Material
Quality Control Test for Glass Container
Quality Control Test For Plastic Container
Conclusion
Reference
•Packaging
Packaging is the science, art and technology of enclosing or protecting
products for distribution, storage, sale, and use.

Production marketing
Role of Packaging:

Protection -against light


-against reactive gases
-against moisture
-against microbes
-against physical damage
-against adulteration

Presentation
Identification
Information
Convenience
Primary packaging
Primary Packaging is the material that first envelops the product and holds it. This
usually is the smallest unit of distribution or use and is the package which is in direct
contact with the contents.
Secondary Packaging
Secondary Packaging is outside the primary packaging perhaps used to group
primary packages together
Tertiary Packaging
Tertiary Packaging is used for bulk handling , warehouse storage and
transport shipping.
◦ Ampoules
◦ Vials
◦ Containers
◦ Dosing dropper
◦ Syringe
◦ Strip package
◦ Blister packaging
• Paper and boards
• Cartons
• Box manufacture
TYPES OF GLASS:
1) Type I ( Neutral or Borosilicate Glass)

Type I

2) Type II ( Treated Soda lime glass)

3) Type III ( Soda lime glass)

4) Type IV ( General purpose soda lime glass)

Type II /III
QUALITY CONTROL TESTS FOR GLASSES
1) CHEMICAL RESISTANT OF GLASS CONTAINERS
A) Powdered Glass Test:
It is done to estimate the amount of alkali leached from the powdered glass which
usually happens at the elevated temperatures. When the glass is powdered, leaching of alkali
is enhanced, which can be titrated with 0.02N sulphuric acid using methyl red as an indicator

Step-1: Preparation of glass specimen:


Few containers are rinsed thoroughly with purified water and dried with stream of
clean air. Grind the containers in a mortar to a fine powder and pass through sieve no.20 and 50.

Step-2: Washing the specimen:


10gm of the above specimen is taken into 250 ml conical flask and wash it with 30 ml
acetone. Repeat the washing, decant the acetone and dried after which it is used within 48hr.
Procedure:
10gm sample is added with 50ml of high purity water in a 250ml flask. Place it in an
autoclave at 121⁰C±2⁰C for 30min.Cool it under running water. Decant the solution
into another flask, wash again with 15ml high purity water and again decant. Titrate
immediately with 0.02N sulphuric acid using methyl red as an indicator and record the volume.
B) Water Attack Test:
This is only for treated soda lime glass containers under the controlled humidity
conditions which neutralize the surface alkali and glass will become chemically more resistant.
Principle involved is whether the alkali leached or not from the surface of the container.

Procedure:
Rinse thoroughly with high purity water.
Fill each container to 90% of its overflow capacity with water and is autoclaved at 121⁰C for
30min then it is cooled and the liquid is decanted which is titrated with 0.02N sulphuric acid
using methyl red as an indicator.
The volume of sulfuric acid consumed is the measure of the amount of alkaline oxides
present in the glass containers.
Test Limits

TESTS CONTAINER VOL.OF 0.02N H2SO4

Type I 1.0
Powdered glass test Type II 8.5
Type III 15.0

Type II (100ml or below) 0.7


Water attack test
Type II (above 100ml) 0.2
2) Hydrolytic Resistance Of Glass Containers:
Rinse each container at least 3times with distilled water and fill with the same to their
filling volume. Heat to 100⁰C for 10min and allow the steam to issue from the vent cork. Rise
the temp from 100⁰C to 121⁰C over 20min. Maintain the temp at 121⁰C to 122⁰C for 60min.
Lower the temp from 121⁰C to 100C over 40min venting to prevent vacuum.

Remove the container from autoclave, cool and combine the liquids being examined.
Measure the volume of test solution into a conical flask and titrate with 0.01M HCl using
methyl red as an indicator. Perform blank with water and the difference between the titration
represents the volume of HCl consumed by the test solution.

Nominal Number of Volume of test solution to be


Capacity Of containers used for titration (ml)
container (ml) to be used
5 or less at least 10 50.0
6 to 30 at least 5 50.0
More than 30 at least 3 100.0
15
03 Thermal Shock Test:
Place the samples in upright position in a tray. Immerse the tray into a hot water
for a given time and transfers to cold water bath, temp of both are closely controlled.
Examine cracks or breaks before and after the test. The amount of thermal shock a bottle can
withstand depends on its size and design. Small bottles withstand a temp differential of 60
to 80⁰C and large bottle 30 to 40⁰C. A typical test uses 45C temp difference between hot and
cold water.

04 Leakage Test:
Fill 10 containers with water, fit with intended closures and keep them inverted at
room temperature for 24hr.The test is said to be passed if there is no signs of leakage
from any container.
The most common instrument used is American glass research increment
pressure tester .The test bottle is filled with water and placed inside the test
chamber. A scaling head is applied and the internal pressure automatically raised by
a series of increments each of which is held for a set of time. The bottle can be
checked to a preselected pressure level and the test continues until the container
finally bursts.
Collapsibility test :
Applicable to containers which are to be squeezed in order to
remove contents. yield 90%of its contents at required rate of flow at ambient
temp.

Clarity of aqueous extract:


Clarity of aqueous extract Select unlabelled portion from a
suitable containers Cut these portions into strips Wash it with extraneous matter by
shaking with two separate portions of distilled water Transfer to flask – previously
washed with chromic acid Rinse with distilled water add 250ml d.w. Cover the
flask autoclave at 121Ċ, 30min Colourless , free from turbidity

Non-volatile residue
Evaporate 100 ml of the extract obtained in the test for Clarity of
aqueous extract to dryness and dry to constant weight at 105º. The residue weighs not
more than 12.5 mg.
Leakage test, Collapsibility test
Same As Describe in Non- Injectable

Clarity and colour of solution


Acidity or alkalinity
Light absorption
Reducing substances
Transparency
Fill a container to its nominal capacity with water and close it, if possible
using the usual means of closure; otherwise close using a sheet of pure
aluminium. Heat in an autoclave so that a temperature of 121 ± 2º is reached
within 20 to 30 minutes and maintain at this temperature for 30 minutes. If
heating at 121º leads to deterioration of the container, heat at 100º for 2 hours.

Use solution S within 4 hours ofpreparation


Blank.
Prepare a blank by heating water in a borosilicate glass flask closed by
a sheet of pure aluminum at the temperature and for the time used for the
preparation of solution S.

Clarity and colour of solution S.


Solution S is clear and is colorless.

Acidity or alkalinity.
To a volume of solution S corresponding to 4 per cent of the nominal
capacity of the container add 0.1 ml of phenolphthalein solution. The solution is
colorless. Add 0.4 ml of 0.01M sodium hydroxide. The solution is pink. Add 0.8 ml
of 0.01M hydrochloric acid and 0.1 ml of methyl red solution. The solution is
orange-red or red.
Light absorption.
The light absorption in the range 230 nm to 360 nm of solution S using a blank
prepared as described under Solution S is not more than 0.20

Reducing substances.
To 20.0 ml of solution S add 1 ml of dilute sulphuric acid and 20.0 ml of
0.002M potassium permanganate. Boil for 3 minutes. Cool immediately. Add 1 g of
potassium iodide and titrate immediately with 0.01M sodium thiosulphate, using 0.25
ml of starch solution as indicator. Carry out a titration using 20.0 ml of the blank
prepared as described under Solution S. The difference between the titration volumes
is not more than 1.5 ml.

Transparency
Fill the container previously used for the preparation of solution S to its
nominal capacity with a 1 in 200 dilution of the standard suspension for
a container made from polyethylene or polypropylene. For containers of
other materials, use a 1 in 400 dilution. The cloudiness of the
suspension is perceptible when viewed through the container and
compared with a similar container filled with water
Fill 5 containers with nominal volume of water and heat seal the bottles with
aluminium foil.

Weigh accurately each container and allow to stand for 14 days humidity-
60±5% temp. 20Ċ and 25Ċ.

Reweigh the containers.

Loss in wt in each container is NMT 0.2%


Thank You

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