This file describes analysis of raw material in pharmaceutical and contain different steps which is to be followed for its analysis

1. ANALYSIS OF RAW
MATERIALS
Presented By- Sk Azizuddin Presented To- Prof.Sandhya Bawa
Subject- Pharmaceutical Analysis
Course- M.Pharm
Batch- 2020-2022
College- Jamia Hamdard
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2. CONTENTS
 Introduction
 Definition
 Types of Raw Material
 Importance of Raw material testing for pharmaceutical.
 Need for Raw material testing
 Purchase specifications
 Control on Raw materials
 Sampling of Raw materials
 Raw Material’s testing
 Storage condition of Raw material
 Reference
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3. Introduction
 Quality assurance (QA) and quality
control (QC) are important in the pre-
production stage of pharmaceutical
production, so as to verify that the raw
materials do not contain impurities that
can cause health hazards or more
complex purifications and lower yields.
 In Raw Material analysis, a variety of QA
and QC analytical instruments to
perform raw material ID using a variety
of different techniques.
 Raw material ID is the process of
evaluating these raw materials to identify
and discard any impurities or adulterants
that could have an adverse effect on the
final product.
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4. Definition
 It is basically the chemical ingredients of a process.
 Basic raw materials are starting material, which is used in production of final
product.
 Raw materials can be either active drug or inactive substances
 The basic material from which a product is made is called as Raw Material.
 Pharmaceutical raw materials are the substances that are used to manufacture wide
range of drug formulations, tablets, capsules, injectable etc.
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5. Types of Raw Material
 Pharmaceutical raw materials include active pharmaceutical ingredients (APIs) and
inactive ingredients or excipients as well as packaging material.
 APIs are bulk drugs that are pharmaceutically active and generate a desired
pharmacological effect, whereas, excipients are pharmacologically inactive substances
that are generally used as a carrier of the API in the drug.
 Excipients are also called drug carries. They are the carrier materials and are definitely
part of any drugs. It is a commonly known fact that the drugs we use contain only a very
tiny part of actual drug that effects the bodily changes. The remaining parts only a
carrier which we call the excipients in pharma terms.
 The pharmaceutical raw materials used for the excipients include solvents and other
carriers which are capable of carrying the actual drug. This excipient should not affect
the chemical features of the API.
 Even the packaging in the pharmaceutical industry have to be prefect and precise. Raw
material used for pharmaceutical packaging include plastic &polymers, glass, paper,
aluminium foil and paper boards etc. These are used in making most of the packaging
used in pharma. Because of the diversified products being used as raw materials, even
packaging is made a separate category.
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6. Importance of Raw material testing for
pharmaceutical
 Raw material testing is crucially important for ensuring safety, quality and
efficacy of pharmaceutical products.
 There are many things to be considered that could impact the way raw
materials need to be blended, such as polymorphism, the particle size of
raw materials and other properties.
 Hence, raw material analysis is essential to determine the purity, identity
and quality of the raw materials before they go into the manufacturing
process.
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7. Need for Raw material testing
 As hundreds of raw materials and ingredients are used in the process of
formulating the final pharmaceutical product, it is quite tough to check
every ingredient for quality.
 Unless the ingredients have undergone quality testing, beginning the
manufacturing process won’t be possible. Moreover, if low-quality raw
materials are used, it will result in a low-quality finished product which
could face product recall.
 This can cause significant damage to material costs as well as reputation.
Therefore, raw material testing in pharmaceuticals is necessary
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8. Ensuring a Quality product
 Pharmaceutical raw material testing is carried out to establish that all the
incoming raw materials match the right specifications and requirements.
Needless to say, incorrect supply of raw materials will lead to a
compromise in the safety and quality of the end product.
 Besides, it will also cause manufacturing delays and significant wastage of
time and costs. Therefore, testing labs help pharmaceutical companies lay
down the specifications for the raw materials right from the initial stages
of drug development.
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9. Testing Labs: Standards and approvals
needed
 Every pharmaceutical product or medical device has to be approved by the
State FDA and the Central Drugs Standards Control Organisation (CDSCO)
before it is rolled out for public use or commercialization.
 Testing laboratories can help carry out material analysis, DSC analysis,
chemical tests, physical characterisation,NMR testing,FTIR testing and more, all
according to the specifications and safety protocols established by the FDA
and CDSCO.
 Traditionally, chemical testing laboratories perform the raw material testing
and prepare the reports to determine their quality and suitability to be used in
pharmaceutical drug formulations. They are well equipped to carry out the
sophisticated procedures involved in raw material tests.
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10. Purchase specifications
 Written guidelines that precisely define the operational, physical, or
chemical characteristics, as well as the quality and quantity of a particular
item to be acquired.
 Mode of purchasing :
 By inspection
 By sample
 By description of brand
 By grading
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11. Steps involved in purchase procedure
 Purchase requisition
 Selection of supplies
 Inviting Quotation
 Placing the order
 Receiving the material
 Checking of invoice or bill
 Recording of bills in books
 Releasing the payment to the supplier
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12. Criteria for raw materials purchase
specification
 It must be noted that pharmacopoeia standards are minimum.
 Where no such stds. are applicable to raw material, the
specifications should include at least requirements for
identification, limits for purity and potency and limits for impurities.
 Where such standard exist for raw material, alternative test
methods may be used but there should be written evidence to
show that such method are at least as precise and specific as the
official methods.
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13. Staff involved in purchasing have a particular and thorough knowledge
of products and suppliers.
Raw material can be purchased from supplier named in relevant
specification or directly from procedure.
Specification established by manufacturer for the starting materials be
discussed with suppliers.
Pharmacist or chemist, who is familiar with quality requirement of
various material purchase department can be head of purchase
department.
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14. As per GMP & WHO guidelines for handling
of raw materials
 On receipt , each delivery of raw materials should be visually examined for labels,
damage to containers.
 Raw materials, then should be transferred to quarantine area and labels over
printed with words under test.
 Quality control for sampling.
 Quality control persons should withdraw the sample from quarantine. While
sampling, the point should be kept in mind :
 sample should be representative of the batches.
 All sampling equipment must be clean.
 On receipt of approval or rejection of the raw material, it should be transferred to
area marked for approved materials or rejected materials.
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15.  Raw material should be stored in clean container.
 Raw material should be stored at optimum temperature and humidity.
 It should be inspected at some intervals.
 It should be stored in such a manner that material received first is issued
first.
 The clean equipment should be used for dispensing.
 Raw materials are used only when are approved by quality control
department.
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16. Preparing A Prospective Supplier List
 We can search for the potential vendors by looking at several information sources :
 Past experiences.
 Interviewing with the salesperson of the supplier.
 Catalogues published by the vendors.
 Trade directories.
 Classifies suppliers according to the products they make.
 Includes names of company personnel, financial status, and location of sales
offices.
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17. Types of suppliers
 In the search for suppliers, all available types that is distributors,
manufacturers, and foreign sources should be considered.
 The number of suppliers to be used should also be considered.
 Trade-offs between price, delivery, and service and community
relations and good will must be weighed when selecting various
types of vendors.
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18. Local VS. National Suppliers
 There are inherent natural advantages to buying from local suppliers whenever
possible.
 Among the most significant are the following :
1. Saving of money when the distance between firms is relatively short.
2. Close proximity permits for communication and service; shorter lead times , and
exchanges .
 There are also considerations that favour national suppliers:
 Low price.
 Large inventory.
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19. Raw Material Control
 There is sufficient management systems in place to control the handling and use of all
raw materials on site.
 The staff is sufficiently informed, instructed , trained and supervised to minimize a
potential human failing during raw material delivery, test and storage.
 The procedures in place to test the suppliers of raw materials ( Audits, supplier history,
reputation).
 Quality assurance should make periodic sanitation and follow up to assure that
deficiencies are corrected.
 Warehouses are the first operational area observed by the auditor to check operational
compliance with cGMP & FDA regulation.+
 Following elements need to be considered when establishing warehouses operation :
 Cleanliness , floors , lighting & SOPs
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20. Sampling Of Raw Materials
 After sampling instrument under laminar flow. They are to be tested on sterile cloths
throughout sampling process to prevent contamination.
 Prior to containers being opened, they need to be marked in numerical order on the outer
container. This identified the container number from which will be taken.
 Sterile jar are marked with marker with the information relating to their type of sample.
 Print out the sampling labels which has the following information.
 Laboratory batch number
 Product description
 Sample type
 Number of samples
 Examine all material containers for damage before sampling. Report any damage to
laboratory manager.
 Don’t touch any material with your hand. Always use appropriate sampling tools.
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21. Sampling of Raw material cont.….
 The analyst should wear gloves for sampling of raw materials.
 Samplers are to clean room with respect to absence of watches,
rings, nail polish etc.
 Before sampling any raw material, read carefully the given
instruction on raw material specifications.
 The air conditioning setting and timer are not to be alter in any way
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22. Raw Material Testing
 Quality Control Raw Material Testing
 Before manufacturing begins, all raw materials must be tested for purity, identity and
quality. Depending on the type of product (tablets and capsules vs. biotech products), as
few as 15-20 to as many as 60 raw materials might be needed for product development.
The extent of raw material testing is determined by the manufacturer. A conservative
approach would be to perform complete analysis of each lot of raw materials received.
 Pharmacopoeia provides monographs for the most commonly used raw materials in the
pharmaceutical industry.
 These monographs detail several different analytical techniques. Karl Fischer moisture
analysis, pH, viscosity and titrations are common but more complex techniques such as
HPLC, GC-MS and ICP-MS are sometimes required.
 The analytical chemistry and microbiology teams can help you with the necessary testing
for raw materials, APIs, finished products, packaging materials and medical devices.
 Testing Services for Raw Materials
 Physicochemical Properties
 Identity and Purity –Small Molecules
 Identity and Purity –Large Molecules
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23. Physicochemical
Properties Testing
Services
 Physicochemical property tests
are integral to the verification,
manufacturing support, and lot
release programs for
pharmaceuticals and biologics.
 It is essential that certain physical
and chemical properties do not
vary between or within lots, as
they can determine critical
compound features like drug
delivery and absorption of the
product in vivo.
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24. Testing Services for Physicochemical
Properties
 Appearance
 pH
 Moisture Content
 Osmolality
 Viscosity
 Optical Activity
 Spectral Analysis
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25. Appearance
 This ensures that all tested solutions are essentially free of visible particulates.
 Physical State
 Colour
 Odour
 pH
 pH will determine whether the sample’s acidity/alkalinity meets the client’s expected
specifications. The pH of a small molecule pharmaceutical or biologic formulation can
significantly affect its stability ,solubility, and in vivo delivery, making this test a crucial
element of any lot release program.
 Moisture Content
 A large variety of pharmaceutical and biologic products contain water as hydrates (water
of crystallization) or in adsorbed form (surface water). The degree of water contained can
influence the therapeutics’ shelf life, activity, and quality, thus requiring compliance to a
predetermined
 Osmolality
 Osmolality is another important factor of lot release for a developed drug and is defined
as the total number of solute particles per kilogram of solvent.
 freezing point technology to test the osmolality of prepared solutions to ensure correct
isotonicity, consistency, formulation, and product stability.
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26.  Viscosity
 A fluid’s resistance to flow, measured as viscosity, is a principal component of lot
conformance.
 Viscosity is fundamental to a formulation’s intended propagation and activity, and may
be used as a benchmark for compound concentration or degradation.
 Optical Activity
 Many pharmaceutical compounds are chiral and hence optically active, given that
rotate plane polarized light.
 The measure of optical activity of the provided solution can then be used by the client
for many different aspects of a lot release program. By comparing with predetermined
target specifications, polarimetry may be used to detect impurities or to determine the
concentration of the intended chiral drug product.
 Spectral Analysis
 The unique absorption spectra of chemical/biochemical products can serve
a distinguishing physicochemical property of pharmaceuticals and biologics.
 Analysis employs Ultraviolet-Visible (UV-Vis) and Fourier Transform Infrared
(FTIR) Spectroscopy for target compound identification and concentration
measurement. Spectral analysis may also be used to reveal impurities in the
yield product.
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27. Identity and Purity –Small Molecules
 Small Molecule Identity and Purity Testing
 Identity and purity testing are crucial requirements of a lot release.
 Testing Services for Identity and Purity
 HPLC (High-Performance Liquid Chromatography) with different detectors
 Mass Spectrometry –LC-MS, LC-MS/MS, and TOFMS
 UV-Vis (Ultraviolet-Visible Spectroscopy)
 FTIR (Fourier Transform Infrared Spectroscopy)
 TLC (Thin-Layer Chromatography)
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28.  HPLC (High-Performance Liquid Chromatography)
 Chromatography describes the use of high-performance liquid chromatography for
qualitative and quantitative analyses.
 This is done by comparing the chromatogram with the reference peak.
 Discrepancies between the expected and experimental chromatograms may indicate
sources of impurity within the lot.
 Mass Spectrometry
 LC-MS (Liquid Chromatography Mass Spectrometry) is an accurate and reliable
of chemical analysis that combines the advantages of liquid chromatography and mass
spectrometry.
 Mass to charge ratios derived from this analytical technique can reveal molecular
of each compound and therefore help with the identification of the analytes and
impurities.
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29.  UV-Vis (Ultraviolet-Visible Spectroscopy)
 Spectrophotometric tests are critical for the identification of many chemical
substances
 These tests yield absorption spectra that demonstrates rough identification
the formulation and any contamination.
 FTIR (Fourier Transform Infrared Spectroscopy)
 Infrared spectroscopy is notably the most powerful test in confirming the
identity of small molecules and pharmaceuticals.
 FTIR results may be used to compare multiple specific peaks in the IR
spectrum with those of a reference standard, establishing a robust
criteria.
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30. Identity and Purity –Large Molecules
 Large Molecule –Identity and Purity Testing
 When manufacturing biological products (large molecules), it is imperative that
each lot produced conforms to predetermined specifications.
 Testing Services for Identity and Purity
 HPLC (High-Performance Liquid Chromatography)
 Mass Spectrometry
 SDS-PAGE (Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis)
 Western Blot
 ELISA (Enzyme-Linked Immunosorbent Assay)
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31.  Mass Spectrometry
 Mass spectrometry can be used to identify biological products and alert the manufacturer of any
impurities.
 SDS-PAGE (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis)
 SDS-PAGE separates out proteins in a polyacrylamide gel based on size.
 Western Blot
 Western blots are conducted by first running an SDS-PAGE gel and then transferring the proteins
onto a membrane.
 This method can be used to identify the protein product or product related impurities.
 ELISA (Enzyme-Linked Immunosorbent Assay)
 ELISA is used to detect proteins and determine the concentration of the protein of interest.
Indirect, direct and sandwich ELISA are the most common variations of ELISA.
 The absorbance readings from each well are compared with the standard curve to determine
concentration of the protein of interest from each sample.
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32. Storage condition of Raw Material.
 Maintenance of Stores
 Storage Area Specifications-:
 Sufficient Capacity
 Clean, Dry and maintained with in acceptable temp.limit
 Designed and equipped reception area
 Ensuring of quarantine status
 Separate sampling area
 Segregation for storage of rejected sample, recalled or returned material
 Safe and secure area for narcotics and highly active , dangerous and risky material.
 First in and first out rule(FIFO)
 First expiring first out(FEFO)
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33. Storage conditions
 Room temp, should be 30 degree Celsius and R.H 60%
 A.C storage (25±2 degree celsius) and R.H 45-55%
 Low temp storage 2-8 degree Celsius
 Separate area for sterile product storage on A.C
 Light sensitive material in amber colour container
 Hermitically sealed container
 Labelling of material in storage area.
 Designed name of product and internal code reference.
 Batch No. given by supplier
 Status of content
 Expiry date or date beyond which refreshing is necessary
 During fully computerized system used, labelling with all above information need not be necessary.
 Check list before storage
 Integrity of package and seal.
 Correspondence note for the order deliver and suppliers labels
 Check list during storage
 Quality of materials
 Released by QC department only.
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34. Reference
 https://www.sandoopharm.com/What-are-the-raw-materials-required-for-
pharmaceutical-industry-id3757212.html
 Google Slide share
 Quality Assurance Book Volume 2 by WHO
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