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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
BIOT 4801 Biotecnologa Operacional I
UIPR BarranquitasJA Negrn, Ph.D.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
ContentContent Raw material management
Quality
Raw materials in a biopharmaceutical environment
Types of materials
Introduction to regulation from FDA
Analytical tests for identity, quality, quantity, and contaminants
AAS, ICP
IR
HPLC
Microbiological
Endotoxins detection Water
Purified water
Water for injection
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
QualityQuality Quality Assurance (QA)
It is the sum total of the organized
arrangements with the objective of ensuringthat products will be of the quality required
for their intended use.
Good Manufacturing Practices (GMP)
QA
GMP
Is that part of Quality Assurance aimed atensuring that products are consistently
manufactured to a quality appropriate to their
intended use.
Quality Control (QC) Is that part of GMP concerned with sampling,
specification & testing, documentation &
release procedures which ensure that the
necessary & relevant tests are performed &
the product is released for use only afterascertaining its quality.
QC
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Quality ControlQuality Control
A process employed to ensure a certain level
of quality in a product or service.
Analysis of raw materials
Analysis finished formulation
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Application of GMP Guidance to API ManufacturingApplication of GMP Guidance to API Manufacturing
http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm200364.htm#P208_6121
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Raw Materials in a Biopharmaceutical IndustryRaw Materials in a Biopharmaceutical Industry
Biological or chemical substances used to manufacture theproduct Chemical reagents
Organic, inorganic
Cell culture nutrients
Detergents Anti foam agents
Enzymes
Cleaning agents
Growth factors Chromatographic media
Other
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Management of MaterialsManagement of Materials
According to the U.S. Federal Drug
Administration FDA, there should be writtenprocedures describing the receipt,
, , , ,
sampling, testing, and approval or rejection of
materials.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Department of Health and Human ServicesDepartment of Health and Human Services
U.S. Food and Drug AdministrationU.S. Food and Drug Administrationhttp://www.fda.gov/http://www.fda.gov/
Responsibility of FDA
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT Guidance for IndustryGuidance for Industry
Q7A Good Manufacturing Practice (GMP) Guidance forQ7A Good Manufacturing Practice (GMP) Guidance forActive Pharmaceutical Ingredients (APIs)Active Pharmaceutical Ingredients (APIs)
Guidance regarding GMP for the manufacturing APIs
Operations of receipt of materialsreceipt of materials, productionproduction, packaginpackaging,repackagingrepackaging, labelinglabeling, relabelingrelabeling, quality controlquality control, releasrelease,
storagestorage and distributiondistribution of APIs and the related controls.
ttp: www. a.gov ICECI Comp anceManua s CompliancePolicyGuidanceManual/ucm200364.htm#P20
8_6121
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Raw Material Sampling and DispensingRaw Material Sampling and Dispensing
Sampling Sampling needs to be done in accordance with
approved written procedures, such as SOPsSOPs(standard operating procedure) in order to avoidand/or detect contamination.
Most of the samples need to be tested and
analyzed for microbial content against the specifiedlimits. So, one has to ensure that during samplingenvironmental microbes do not contaminate thesamples drawn.
Dispensing
Accuracy of weighing is very critical, as any of theweighing errors will affect the composition of finalproduct.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Verification of Raw MaterialsVerification of Raw Materials Incoming raw material should not be used until it has been
inspected and verified as conforming to the specifiedrequirements.
This verification should be in accordance with therequirements of the quality plan or other documented
.
This verification should include a check that: the labels indicate that it is the item ordered
the containers are not damaged and all seals are intact
materials and packaging components received do correspond to
the items ordered there is no evidence of alteration and that the delivery generally
appears to be in good condition and suitable for use
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Sampling and Testing of IncomingSampling and Testing of IncomingProduction MaterialsProduction Materials At least one test to verify the identity of each
batch of material should be conducted Complete analyses should be conducted on at
least three batches before reducing in-house
testing. Supplier's certificate of analysis
Sometimes can be use in place of additional tests
Certain materials and in certain circumstances areexempted from analysis if manufacturer'scertificate of analysis is obtained.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
What may be required in a Certification of Analysis?What may be required in a Certification of Analysis?1. Name and Address of Certifying Body
2. Title of Document
3. Description of Material
4. Reference Material Code and Batch Number
5. Description of Certified Reference Material (CRM)
6. Intended Use
'
8. Hazardous Situation9. Level of Homogeneity
10. Certified Values and their Uncertainties
11. Traceability
12. Values Obtained by Individual Laboratories or Methods
13. Uncertified Values
14. Date of Certification
15. Period of Validity
16. Further Information
17. Names and Signatures of Certifying Officers
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Example of aExample of a
Certificate of AnalysisCertificate of Analysis
http://www.elannutrition.com/
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Raw Material AnalysisRaw Material Analysis Atomic Absorption
Spectroscopy (AAS) Infrared
Spectroscopy (IR) Portable Raman Spectrophotometer
HPLC Gravimetric analysis
Microbiological tests
Endotoxins analysis(LAL)
laser: 120mW 785 nm resolution: 8 cm-1
spectral range: 200 - 2000 cm-1
http://deltanu.com/inspector-raman/
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Essential trace elements -Fe, Cu, Zn, Cr, Se, Ca,
Mg, Co, Mo, I, Si, and Mn
Toxic elements -Cd, Mo, Pb, Hg, As, Sn,
ass e ementa mpur t es s, an g Class 2 elemental impurities are metal
catalysts, which include Cr, Cu, Iridium, Mn,
Mo, Ni, Os, Palladium, Pt, Rh, Ru, and Va.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Atomic Absorption Spectroscopy (AAS)Atomic Absorption Spectroscopy (AAS) Atomic absorption spectrometers use light absorption to measure the
concentration of gas-phase atoms.
It is the most common method to analyze metals and metalloids.
Technologies
Flame atomic absorption spectroscopy (FAAS)
Graphite Furnace atomic absorption spectroscopy (GFAAS)
Inductively Coupled Plasma (ICP)
Elements detectable by atomic absorption are highlighted in pink in this
periodic table:
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Flame Atomic AbsorptionFlame Atomic Absorption
Spectroscopy (FAAS)Spectroscopy (FAAS)
Atomic Absorption is the process where vaporized atoms
absorbs light and is measured. During combustion, atoms of the element of interest in the
sample are reduced to free, unexcited ground state atoms,
.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Graphite Furnace Atomic AbsorptionGraphite Furnace Atomic Absorption
Spectrometry (GFAAS)Spectrometry (GFAAS) Electrothermal atomisation
It requires a graphite furnacegraphite furnace, where after thermal pre-treatment the
sample is rapidly atomized. Graphite furnace atomic absorption spectrometry is a highly sensitive
spectroscopic technique that provides excellent detection limits formeasuring concentrations of metals in aqueous and solid samples.
metals in aqueous solutions. Better detection limits for GFAAS. For example Pb by FAAS ~ 0.19
mg/L Pb by GFAAS ~ 0.012 ng/mL
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Inductively Coupled Plasma (ICP)AtomicInductively Coupled Plasma (ICP)Atomic
Absorption SpectrophotometerAbsorption Spectrophotometer
Inductively Coupled Plasma (ICP) - Plasma
Acoplado por Induccin
Better sensitivity and detection limits than FAAS.
.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Detection Limits of Various AtomicDetection Limits of Various Atomic
SpectroscopicalSpectroscopical TechniquesTechniques
DetectionDetection LimiLimitmean the lowest concentration that could be detected.
FAASFAAS (Flame Atomic Absorption Spectroscopy), ICPICP--AESAES (Inductively Coupled Plasma
Atomic Emission Spectroscopy), GFAASGFAAS (Graphite Furnace Atomic AbsorptionSpectroscopy, ICPICP--MSMS (Inductively Coupled Plasma Mass Spectrometry)
ICP-MS
0.0001 0.001 0.01 0.1 1.0 10 100 1000
FAAS
ICP-AES
GFAAS
Analyte concentration in g/L (ppb)1g/1L = 1ppt
1mg/L =1ppm1g/L = 1ppb
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Example of Raw Material AnalysisExample of Raw Material Analysis Distinguishing different
polymorphs of lactoseusing Nearinfrared(NIR) spectroscopy
influence flowproperties andmoisture uptake, whichin turn affect blend andcompression behaviour
http://pharmtech.findpharma.com/pharmtech
/Analytical/Ensuring-raw-material-
quality/ArticleStandard/Article/detail/583766
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Example of Raw Material AnalysisExample of Raw Material Analysis NIR spectra of
microcrystallinecellulose of threedifferent particle sizes.
particle size can resultin a poor performanceduring the process,due to difference inparticle in this rawmaterial.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
HPLC (High performance liquid chromatography)HPLC (High performance liquid chromatography)
Is one of the most powerful tools inanalytical chemistry.
It has the ability to separate, identify, andquantitate the compounds that are present inany sample that can be dissolved in a liquid.
Trace concentrations as low asparts pertrillion [ppt] may easily be identified.
HPLC can be, and has been, applied to justabout any sample, such as pharmaceuticals,
food, nutraceuticals, cosmetics,environmental matrices, forensic samples,and industrial chemicals.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
The Basic Liquid ChromatographThe Basic Liquid Chromatograph
The basic liquid chromatograph consists of six
basic units:
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Detectors used in HPLCDetectors used in HPLC UV-vis -10pg
Fluorescence 10fg Refractive Index (RI) 100pg
FTIR 1g
Electrochemical (EC) -100pg
amperometric
NMR novel
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Viable Microorganisms in Raw MaterialsViable Microorganisms in Raw Materials
Mainly aerobes
Microbial limit testing of raw materials-BioburdenBioburden Defined as the quantitative estimation of
the number of viable microorganisms in
material before sterilization. According to standards
Such as USP United StatesPharmacopeia
Example Opportunistic organism such as
Salmonella sp., E. coli, Staphylococcusaureus and Pseudomonas aerginosa
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
EndotoxinsEndotoxins Endotoxins are compounds
found in the cell walls of Gram
negative bacteria. These compounds help to form
a semi-permeable membrane
bacteria from threats. Once the bacteria die, the
endotoxins are released, andmany of these toxins cause
health problems in people,animals, and other organisms,hence the toxin in their name.
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
EndotoxinsEndotoxins Small, stable, bacterially-
derived hydrophobic
molecules which can easily
contaminate labware and
whose resence can
significantly impact both invitro and in vivo experiments.
Detected by the limulus
amebocyte lysate (LAL) assay
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mmed&part=A289
(Horseshoe Crab)
Limulus polyphemus
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Water used in the industryWater used in the industry1. Water treatment
systems
2. Storagerequirements
.
4. Different types ofwater used inpharmaceuticals
5. Microbial limits,disinfection
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
WaterWater Industry utilizes batch type reactions to
manufacture its products. Cleanliness is an important factor since the
roducts are eventuall consumed b humans.
Water requirements depend on theapplication
Purified water general form
Water for injection (WFI) more stringentrequirements
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
Purified Water vs. Water for InjectionPurified Water vs. Water for Injection
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RAW MATERIAL MANAGEMENTRAW MATERIAL MANAGEMENT
ReferencesReferences Halsey, S. 2009. Ensuring raw material quality.
PharmTech. * From:http://pharmtech.findpharma.com/pharmtech/Analytical/Ensuring-raw-material-quality/ArticleStandard/Article/detail/583766
John, B.A., K.C.A. Jalal, Y.B. Kamaruzzaman and K. Zaleha,
crab blood during bacterial endotoxin invasion. J.Applied Sci., 10: 1930-1936. (en reserva digital)
Riley, B.S. 2004. Rapid microbiology methods in the
pharmaceutical industry. Pharmaceutical Review.* (en
reserva digital)
http://www.fda.gov/
*Artculos asignados para el primer examen parcial.
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