1. RAW MATERIALS, SPECIFICATION OF
MATERIALS AND FINISHED
PRODUCTS
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P R E PA R E D B Y: K E Y U R R . P R A J A PAT I
M.PHARM SEM-I (Q . A)
G U I D E D B Y : M R . A N A N D K . PAT E L
D E PA R T M E N T O F Q . A
A . P. M . C . C O L L E G E O F P H A R M A C Y
H I M M AT N A G A R
2. CONTENET
Introduction
Raw material
• Purchase specifications,
• Maintenance of Stores,
• Selection of Vendors,
• Control on raw materials and finished dosage forms
Specification of finished products
• Introduction
• General concepts
• Specifications for the finished product
• Specifications for documentation of the finished
product
• Specifications for storage of the finished product
• Generally acceptable specifications for drug products
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3. INTRODUCTION
GMP:
“Good Manufacturing Practice is a set of regulations, codes,
and guidelines for the manufacture of drug substances and
drug products, medical devices, in vivo and in vitro
diagnostic products, and foods.”
Raw materials:
“It is the starting material used in the manufacture of
finished product”
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4. Principle
Objective of the pharmaceutical manufacturer
produce finished products for patient's use from a
combination of materials
Materials combined
Active pharmaceutical ingredients and
Excipients (auxiliary materials)
Packaging materials
Materials include also
Gases, solvents, reagents, process aids, etc.
Special attention
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5. General requirements for materials
Materials for cleaning, lubrication, and pest control
Not in direct contact with product
Suitable grade, e.g. food grade if possible
All incoming materials and finished products
quarantined after receipt or processing
until released for use or distribution
Maintenance of stores
Good state of repair: Walls, Ceiling Paint, Plumbing,
Electrical damages
Protection from light and Exposure to air
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6. Storage specification
• under appropriate conditions
• orderly fashion (batch segregation)
• materials management
• stock rotation (FEFO)
Water – suitable for use
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7. Starting Materials
Purchasing Specifications:
important –highly techno commercial operation
From approved suppliers – if possible, direct from the
manufacturer
Vendor selection and certification
Consistency of Quality
Capacity of plant for Volume Requirements
Consistency of price
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8. Inventory management:
Material management
The ABC concept
Economical lot size or order quantity(EOQ):
EOQ can give us optimum quantity which should be
ordered for purchasing and at this point balance is
reached between the factor i.e. acquisition cost and
carrying cost
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9. Where, A=annual or periodical requirement
O=ordering cost
C=carrying cost per unit
Consignment checks
Integrity of package
Seal intact
Corresponds with the purchase order
Delivery note
Supplier’s labels
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10. Cleaned and labelled with information
Examples of Labelling of Starting Materials
Fully computerized storage system
Name of
Material and/or
internal code
Control/
Batch No.
Quarantined/Released/Rejected
Status
(Colours may be used)
Expiry date or
retest date
Date Signature
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11. Appropriate measure to ensure identity of
contents of materials
Use only QC released material if within shelf-life
Dispensing
designated persons
written procedure
Correct materials accurately weighed
clean, properly labelled containers
Independent checks and record
material and weight or volume
Dispensed material
kept together and labelled
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12. Packaging materials
Type of packaging materials:
Primary packaging materials
Secondary packaging materials
Printed and Unprinted packaging materials
Each delivery or batch: specific reference number or
identification mark
Delivery to packaging department
Check quantity, identity and conformity to packaging
instructions
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13. Outdated or obsolete material
Destroyed
Disposal record
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14. Vendor selection and Evaluation
This SOP describes the procedure to be followed during the
vendor assessment and vendor evaluation for purchasing of
raw materials, critical and non critical packaging
components, laboratory supplies, engineering supplies and
imported finished goods from the vendor.
These instructions are essential for approving prospective
vendor.
The SOP doesn’t describe the process of selection of a
contract Manufacturer.
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15. The Process of vendor assessment and evaluation is
divided into four phases.
Vendor Assessment/Selection
Phase 1: Technical discussion
Phase 2: General Vendor Audit
Phase 3: Item specific evaluation
Vendor Evaluation
Phase 4: Ongoing vendor evaluation
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16. Vendor certification
This procedure aim to describe the process by which a
vendor may be certified to supply materials or services.
This procedure applies to vendors that supply a material
or service to be used at any stage of manufacture by
operations.
Here you will get the roles of each department in the
process to certify an approved vendor.
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17. Need to source
new vendor is QA, Technical,
Procurement liaise for Identify possible
identified
vendor vendors
Phase 3:
Send Supplier
YES NO Questionnaire
Item specification Accepted
Evaluation
Purchase,
Sampling and
Accepted General Vendor Testing
Audit
NO
Vendor YES
certification
Phase 4: YES NO
YES Phase 2: Discussion to
required proceed
Accepted
NO 17 17
18. Specifications
Authorized, approved, signed and dated
Starting, packaging materials and finished products:
include tests on identity, content, purity, quality
Intermediates and bulk
Water, solvents and reagents
QC, QA or documentation centre
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19. Specifications: Starting and packaging materials
Include:
Name (e.g. INN) and internal code
Pharmacopoeia (if applicable)
Qualitative and quantitative requirements and limits
Other data may include:
Supplier
Sampling procedure or reference
Storage conditions, precautions
Retest date
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20. Quality control of raw material and finished
product
Retest Dating of Raw Materials
The purpose of this procedure is:
to describe how to run the expired stock report; to describe
how to define the requirements for the retesting and assignment
of storage period for active ingredients, excipients and raw
materials;
to instruct retesting procedure and to determine the status of a
finished goods batch with a shorter shelf life.
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21. Archiving Laboratory Documentation
This procedure describes retention and disposal procedures of
laboratory documentation, general laboratory documentation
system that includes
handling of rejected raw material and finished product
reports,
finished goods certificate of analysis,
finished goods register,
raw material certificate of analysis,
procedure for long term document retention.
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22. Raw Materials-Laboratory Testing and
Documentation
This SOP describes the procedure for
sampling,
location,
pre-testing,
testing and documentation of all raw materials and
components subject to test,
out of specification results,
microbiological tests and
release procedure for passed raw materials and components.
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23. Finished Goods-Laboratory Testing and
Documentation
This SOP describes the procedure for
sampling, location, pre-testing,
testing and documentation of all finished products subject to
test,
reagents and standards to be used for analysis,
management of out of specification results,
microbiological tests and
release procedure for passed finished goods.
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24. INTRODUCTION
SPECIFICATION:
“Defined as list of tests, references to analytical
procedures, and appropriate acceptance criteria which
are numerical limits, ranges or other criteria for the
test described.”
It establishes the set of criteria to which the drug
substance, drug product or material at any stages of
manufacture should conform that they are acceptable
for their intended use.
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25. It describes in detail the requirements with which
products or materials used or obtained during
manufacturing have to conform.
Conformance to specification means that the drug
substance and drug product ,when tested according to the
listed analytical procedures will meet the acceptance
criteria.
Finished product:
A pharmaceutical product that has under gone all stages of
production and quality control including being packaged in
its final container and labeled.
Finished product should be held under quarantine until their
final release ,after which they should be stored as usable
stock under conditions established by manufacturer.
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26. Types of specifications
Raw material specifications
Container closure specifications
Finished product specifications
Finished product specifications
Release specifications:
The combinations of physical, chemical, biological and
microbiological test requirements that determine whether a
drug product is suitable for release at the time of manufacture.
Stability indicating specifications:
The combination of physical, chemical, biological and
microbiological test requirements that the active ingredients
or a drug product must meet during its shelf life
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27. OBJECTIVE OF THE
SPECIFICATIONS
The objective of specifications is to assure that each unit
contains the amount of drug claimed on the label, that all the
drug in each unit is available for complete use ,that the drug
stable in the formulation in its specific final container for
its expected shelf life ,and that it contains no toxic foreign
substance
It provide guideline on the setting and justification of
acceptance criteria and the selection of test procedure for new
drug substances of synthetic chemical origin and new drug
product made for them, which have not previously been
registered in any of the pharmacopoeia.
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28. GENERAL CONCEPTS
Periodic and skip testing
Release versus shelf life acceptance criteria
In process tests
Design and development considerations
Parametric release
Alternative analytical procedures
Pharmacopoeial tests and acceptance criteria
Evolving technologies
Reference standard
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29. SPECIFICATIONS ON THE
FINISHED PRODUCT
I) Areas in which Quality characteristics covered by the
specifications:
General characteristics
Identification & assay
Purity tests
Pharmaceutical tests
Safety tests
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30. II) Relationship between dossier specifications and
the Pharmacopoeia:
The general provisions of different
Pharmacopoeias describe and define the
content and legal weight of the various sections of
its monographs and general methods.
The applicant Should determine the most
appropriate means for reaching stated objective.
Monographs represents the limit values of
medicinal product at the end of their shelf life.
Specification must comply with stated
acceptance criteria.
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31. III) Relationships between the specification of a finished
product at the end of shelf life and at manufacture (at
release):
Aim of dossier for a marketing authorization to set
quality level of the medicinal product as intended for
marketing
Shelf life and storage conditions proposed on the
basis of level of active ingredient and level of any
break down products.
The specification limits of the finished product at the
time of batch release are set such that the
specifications proposed at the end of shelf life are
guaranteed.
The specifications of the finished product at
manufacture may be different from those of the
medicinal product at expiry.
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32. IV) Specifications and routine tests for the release of batches of
finished product at the time of manufacture (at release) :
Relationship between validation of the manufacturing
process, GMP and establishment of specifications.
Routine tests and periodic tests. Different type of tests.
Scheme for verifying specifications
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33. V) Acceptance limits :
Acceptance limits of pharmaco technical
parameters
Maximum acceptable deviation in the content of
active substances “unless there is appropriate
justification”
Acceptance limits for excipients.
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34. SPECIFICATION FOR DOCUMENTATION
OF FINISHED PRODUCT
Designated name of the product and the code reference where
applicable.
Designated name(s) of the active ingredients(s).
Formula or reference to formula.
Dosage form description and the package details
Directions for sampling and testing or a reference to procedures.
Quantitative and qualitative requirements with acceptance limit.
Storage conditions and precautions where applicable.
Shelf life.
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35. SPECIFICATIONS FOR STORAGE
OF FINISHED PRODUCT
Should be held in quarantine until their final release
Separate area should be provided for the storage
Stored according to their dosage form
Storage areas should have adequate height and ventilation,
adequate storage equipment .
Adjacent to finished product area, an assembling and
packaging area may be provided.
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36. GENERALLY ACCEPTABLE
SPECIFICATIONS FOR DRUG PRODUCTS
General:
Organoleptic properties (appearance, color, odor)
Identification
Purity
PH
Moisture content
Abnormal toxicity
Specific
Capsules
Emulsions
Tablet
Oral solutions and suspension
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37. Oral powders
Metered dose inhalation aerosols
Topical and ophthalmic preparation
Small volume parenterals
Large volume parenterals
Suppositories
Drug additives
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38. REFERENCE:
1. Good manufacturing practices for pharmaceuticals. 4th
edition ,Sidney H.Willig , James R.Stoker, Marcel
Dekker INC. Page no.386-401
2. cGMP ,documentation and validation, Prof. Manohar
A.Potdar, PharmaMed press, Page no.113-149,354-360
3. Pharmaceutical dosage forms: Parentral medications
Volume 3,2nd edition ,Edited by Kenneth E.Avis,Herbert
A. Lieberman, and Leon Lachman ,Marcel Dekker INC.
Page no.58-62
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39. 4. Pharmaceutical dosage forms: Tablets, Volume 1,2nd
edition ,Edited by Herbert A. Lieberman, Leon Lachman
and Joseph B. Schwartz , Marcel Dekker INC. Page
no.548-551
5. QA Manual by D.H.shah,Pp:125-149
6. Industrial Pharmacy, edited by Herbert A. Lieberman,
Leon Lachman ,page no.747-756
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