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Orientation and Training

Food and Drug Administration

DOCUMENT NO.:

IV-03

VERSION NO.:1.4

Section 3 - Drug Analysis

EFFECTIVE DATE: 10/01/2003 REVISED: 12/31/2007

3.4 Pharmaceutical Chemistry

The exercises that follow are presented as modules providing examples of the techniques needed to analyze a variety of pharmaceuticals in a variety of dosage forms according to the associated Program Assignment Code (PAC).

3.4.1 Pharmaceutical Products Overview

The following outline serves as a guide in developing and customizing a drug training program by delineating pertinent knowledge areas and concepts with which a drug chemist needs to be familiar.

USP <   > refers to the General Chapters - General Tests and Assays , General Requirements for Tests and Assays found in the back of the USP/NF.

  1. Modern Pharmacology
  2. How a New Drug is developed
  3. Standards (USP <11>)
    1. Working
    2. USP
    3. NIST
    4. Other Pharmacopeial Standards
  4. Controlled Substance--DEA Schedule
    Schedule I, II, III, IV, V (USP 23/NF18, (1995), <1076> 'Controlled Substances Act Regulations') or earlier editions of USP/NF.  Note: Later editions of USP/NF do not contain this section, however, the information is available in 21 CFR Part 1308: Schedule of Controlled Substances
  5. V.   How Drugs Work - drugs and receptors
  6. Overview of the Chemistry of Organic Pharmaceuticals
    1. Basic Drugs and their Salts
    2. Acidic Drugs and their Salts
    3. Neutral Drugs
    4. Biotechnology Developed Drugs and Biopharmaceuticals (USP <1045> )
  7. Drug Formulations   (USP <1151> Pharmaceutical Dosage Forms) 
    1. Tablets (immediate and extended release)
    2. Capsules (soft and hard gelatin)
    3. Liquid Products (solutions, elixirs)
    4. Topical Products (creams, ointments, gels, lotions)
    5. Injectionables  (single and multidose)
    6. Transdermal patches and implants
    7. Other products (inhalation, aerosols,  suppositories as listed in USP)
  8. Types of Pharmaceuticals
    1. Analgesics
    2. Antianxiety - sedative, hypnotic
    3. Antiemetic
    4. Local anesthetics
    5. Antibiotics
    6. Antiviral
    7. Other
  9. Fillers, Excipients & Inert Materials used in Pharmaceuticals (USP <1074>)
    1. bulking materials and fillers
    2. lubricants
    3. colorants
  10. Drug Programs and Sample Types in FDA
    1. Compliance  Samples: PAC 56002.
    2. Surveillance Samples: PAC 56008A, C, D, & G.  
    3. New Drug Applications (NDA): PAC 46832.
    4. Abbreviated New Drug Applications (ANDA): PAC 52832.
    5. Consumer Complaints: PAC 56R801.
    6. Shelf-Life Extension Program: PAC 88R_ _ _.
    7. Import Samples: PAC 56008H & J.
    8. Method Validation Samples other than NDA/ANDAs. 
    9. Other Program Samples: PAC 56021, 56021A & B, 56022A, 61003, 63001.

A.  Questions

  1. When would you use a USP standard and when would you use a working standard?  What is needed for working standards that is not needed for USP standards and why?
  2. What is the procedure in the laboratory for obtaining USP standards? NIST standards? Controlled drug standards? 
  3. Describe the differences between an immediate release tablet/capsule, an extended release tablet/capsule and a delayed release tablet. How would someone classify transdermal patches and implants?
  4. What items would likely be found in compressed tablets and what are their purpose? In  capsules? Name at least three items.
  5. Describe to find where to find the PAC code for a product.

3.4.2 Instrumentation and Technique

3.4.2.1 Basic Analytical Techniques

A. Objective

To review and use very basic analytical techniques and equipment routinely used in the laboratory (listed below). The student is expected to read and become familiar with the following techniques as described in the USP. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  • Volumetric Glassware (care, usage and calibration) (USP <31>[volumetric apparatus] and  <841> [Specific Gravity] ),
  • Balances and Weights (general, analytical, micro analytical) (USP <41> ),
  • Thermometers (mercury, alcohol, thermocouple) (USP <21> ),
  • pH (calibration and use) (USP <791> ),
  • Melting Range/Temperature (USP <741> ),
  • Gravimetric  (USP <281> [Residue on ignition] and <271> [Readily Carbonizable Substances Test] ),
  • Titrations (aqueous and non-aqueous, pH, potentiometric),
  • Water Determination (loss on drying and KF titration, USP <921> ),
  • Identification - Organic Nitrogenous Bases (USP <181>)
  • Disintegration Test (USP <701> ),
  • Limits Tests (USP <231>[Heavy Metals] ), and
  • Uniformity of Dosage Units (USP <905>),

B. Exercises

Note:  These tests may be performed in conjunction with other sub-sections of this section and need not be performed in order.

  1. For the following exercises use product #1. 'Acetaminophen (API)' identified in Appendix 1.
    • Melting Range/Temperature (USP <741>),  part 1.2,
    • Gravimetric  (USP <281> [Residue on ignition] and <271> [Readily Carbonizable Substances Test] ),   parts 1.4 and 1.11,
    • Water Determination (Method I, USP <921> ),  part 1.3,
    • Qualitative Chemical tests (USP  <181> ),  parts 1.5, 1.6, 1.7, 1.9,  and 1.10, and
    • Limits Tests (USP <231> [Heavy Metals]), parts 1.8. 
  2. For the following exercises use product #2. 'Ascorbic Acid Tablets' identified in Appendix 1.
    • Titrations (aqueous)   Assay part 2.1,
    • Dissolution Test, Procedure for a Pooled Sample <711>, and  Disintegration Test (USP <701> ) Use USP 23,  part 2.3 (if apparatus is available)
    • Uniformity of Dosage (USP <905> [Weight Variation] ),  part 2.5, and
    • Identification Tests A, B, C, part 2.2.
  3. For the following exercises use product #8. 'Dextrose' identified in Appendix 1.
    • Water Determination (Method III) USP <921>,   part 6.5,
    • Acidity - Titration (aqueous - limit test),  part 6.4,
    • Identification - precipitate,   part 6.1, and
    • Color of Solution   - part 6.2.
  4. For the following exercise use product #7 'Saccharin' identifies in Appendix 1
    • Titration (aqueous) - part 7.11

C.  Questions

  1. What other standard techniques can be used for determining Melting Range and why are these used? What standards are used for calibration of the Apparatus?
  2. Why are limit and qualitative tests added to USP monographs? Compare the limit tests of the Acetaminophen product with those found in the Dextrose (including those not run). Which tests use the same method?
  3. Both the Acetaminophen product and Dextrose have a method for Water. What is the difference between the two methods?  Can Acetaminophen method be used for Dextrose? Can the Dextrose method be used for Acetaminophen? Explain  the answers.
  4. Look at the USP general section on heavy metals <231>. What is the analyte of interest? Explain why Method I is used for Dextrose while Method II is used for Acetaminophen.

3.4.2.2 Spectrophotometric Techniques

I.   Ultraviolet/Visible Spectrophotometry (USP <851>)

A. Objective

To learn or review essentials of quantitative UV/VIS spectrophotometry and to operate spectrophotometers in the laboratory for drug analysis (topics outlined below). The student is expected to read and become familiar with the following techniques as described in the USP or other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory
    1. Essentials of spectrophotometry
      1. Ultraviolet Range
      2. Visible Range
      3. Near Infrared Range
    2. Linearity
    3. Limitations
    4. Effects of solvent, pH and concentration
  2. Instrumentation
    1. Components:
      1. Source - Tungsten-halogen, Deuterium
      2. Monochromator - Single path, dual monochromator
      3. Sample compartment.- cuvettes (silica, glass, plastic)
      4. Detector 
      5. Photomultiplier
      6. Diode & Diode Array  
    2. Calibration Procedures
    3. Data Collection and Handling
      1. Data Collection Systems
      2. Evaluating Spectra and Data
      3. Qualitation 
      4. Quantitation
      5. Data Storage

B. Exercises

  1. Run holmium oxide filter and compare wavelengths obtained with listed values.
  2. Run potassium dichromate solutions and compare to listed values.
  3. Using several standard solutions from the drug exercise below, check the linearity of the instrument in a range of 0.1 AU to 2.0 AU.
  4. For the following exercises use product 1, 'Acetaminophen (API)' identified in Appendix 1.
    • Identification Test B, UV <197U>, part 1.1, and
    • Assay - UV, part 1.13

C.  Questions

  1. Define: absorbance, absorptivity, molar absorptivity.
  2. What are the typical cell size, specimen concentration and absorbance range used in the analysis of a substance in the UV or visible range?
  3. What do the expressions "similar preparation" and similar solution" indicate (as used in tests and assays involving spectrophotometry in the USP)?
  4. What do the expressions "concomitantly determine" and "concomitantly measured" indicate (as used in tests and assays involving spectrophotometry in the USP)?
  5. 5.Good practice demands that comparisons be made at the wavelength at which peak absorption occurs. What difference in nm for the wavelength specified in the USP monograph is considered acceptable?  

II. Fourier Transform Infrared Spectrophotometry (FTIR) [USP <851>]

A. Objective

To review the theory, instrumentation and proper techniques for FTIR sample preparation and analysis in the drug laboratory (topics outlined below). The student is expected to read and become familiar with the following techniques as described in the USP, other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory
    1. IR radiation
    2. Bonds
    3. Vibrations
    4. Resultant peaks
  2. Instrumentation
    1. Prism
    2. Grating
    3. Fourier Transform
  3. Sampling Techniques
    1. Nujol Mull
    2. KBr pellets
    3. Liquid cell
  4. FTIR instrument operation - Software -Programs, Macros
    1. Calibration
    2. Collect data
    3. Overlay
    4. Library Search
    5. Quantitation
  5. Inspectional Aspects
    1. Calibration
    2. Quality of Spectra
    3. Accuracy

B. Exercises

  1. Scan the IR spectrum of a thin (1.5 mil) film of standard polystyrene polystyrene film and compare the major peaks (see below) with the IUPAC standard polystyrene spectrum.

    3026.27 cm-1  + 2 cm-1

    2849.9 cm-1  + 2 cm-1

    1601.0 cm-1  + 2 cm-1

    1027.7 cm-1  + 2 cm-1

    906.5 cm-1  + 2 cm-1

  2. For the following exercises use product 1. 'Acetaminophen (API)' identified in Appendix 1.
    • Identification Test A, Infrared <197K>, part 1.1
  3. Use the library function of the FTIR, if present, to compare spectra with that in the library data base.  

C. Questions

  1. What is FTIR?
  2. What is the advantage of an FTIR spectrometer (interferometer) over a conventional (dispersive) spectrometer (with a prism or grating monochromator)?
  3.   What is the purpose of the interferometer in the FTIR spectrometer?
  4. List the types of sample preparation techniques used for analysis with an FTIR spectrometer and conventional/dispersive spectrometer, and explain when they would be used.

III. Optical Rotation/Polarimeter  [USP <781>]

A. Objective

To review the theory, instrumentation and proper techniques for optical rotation sample preparation and analysis in the drug laboratory (topics outlined below). The student is expected to read and become familiar with the following techniques as described in the USP, other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory
  2. Instrumentation
  3. Sampling Techniques  
  4. Operation of Instrument

B. Exercises

  1. Check instrument calibration with solid phase calibrator.
  2. For the following exercises use product 8. 'Dextrose' identified in Appendix 1.
    • Specific rotation,   part 8.3, and
    • Assay (use procedure for Dextrose Injection),  part 8.13

C.  Questions

  1. Describe polarimetry and the types of products for which it is used.
  2. What is the purpose of the solid phase calibration cell and how is it used?
  3. What is the general equation used in polarimetry and how does temperature effect polarimeter readings?

3.4.2.3   Chromatographic Techniques

Chromatography is a physical method of separation in which the components to be separated are distributed between two phases, one of which is stationary (stationary phase) while the other (the mobile phase) moves in a definite direction. The ultimate limits in efficiency, for all chromatography (and all separations), are set by the rates of mass transport within the system. A chromatographic system typically consists of several components.

I.  Column Chromatography [USP <621>]

A. Objective

To acquaint the analyst with the underlying principles of column chromatography as a basis of all chromatographic techniques used for drug analysis (topics outlined below). The student is expected to read and become familiar with the following techniques as described in the USP, other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory
  2. Column Types
    1. Celite or Cellulose packed in Glass
    2. Solid Phase Extraction Columns (SPE) - Sep-Pak
    3. Gel
    4. Ion Exchange
  3. Sampling Techniques

B. Exercises (Do one of the three depending on equipment located in the laboratory)

  1. See Laboratory Information Bulletin (LIB) # 3357 and # 2571. Prepare a glass column packed with Solka-Floc material. Separate a color sample product such as grape juice or a mixed standard using the column and method cited. Collect each color and determine their identity using UV-Vis Spectrophotometry
  2. See LIB # 3420 and # 2610. Separate a color sample product such as grape juice or a mixed standard using the column and method cited. Collect each color and determine their identity using UV-Vis Spectrophotometry.

C.  Questions

  1. When and why would someone use column chromatography?
  2. (To be done at completion of each chromatography sections.). Prepare a chart, comparing and relating each of the techniques used in chromatography for the following:  column materials, separation theory, phases, equipment needed, ease of use, accuracy, sampling and sampling techniques, automation, accuracy and quantitation.

II. Thin Layer Chromatography (TLC)   [USP <621> and <201>]

A. Objective

To acquaint the analyst with the underlying principles of Thin Layer Chromatography, (a form of planar chromatography) and the equipment and techniques used for presumptive identification/semi-quantitation of drug samples (topics outlined below). The student is expected to read and become familiar with the following techniques as described in the USP or other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory
    1. Definitions of Terms 
      1. Adsorbent   
      2. Solvent front 
      3. Rf  value      
      4. Origin         
      5. Eluent
  2. Types
    1. Silica Gel
      1. Binders
      2. Fluorescent Additives
    2. Cellulose
    3. High Performance (HPTLC)
  3. Sampling Techniques
  4. Application Techniques

B. Exercises

  1. For the following exercises use product 1. 'Acetaminophen (API)' identified in Appendix 1.
    • Identification Test C. <201>,  part 1.1
  2. Spot above sample or standard at several orders of magnitude of concentration. For example, 1ul, 2ul, 5ul, 10ul, 20ul, 50ul, 100 ul, 200ul, and 500ul.

C.  Questions

  1. TLC is a qualitative method. How can someone use this technique as a semi-quantitative tool? As a quantitative tool?
  2. The exercise uses UV light as a visualizing tool. What other visualizing tools are commonly used for TLC?
  3. In exercise 2 above, what was the smallest spot seen? In the larger spots, were other 'breakdown' or 'related substances' spots seen in the chromatogram?  If found, can the quantity be estimated based on the size of the smaller standard spots?
  4. (To be done at completion of each chromatography sections). Prepare a chart, comparing and relating each of the techniques used in chromatography for the following:  column materials, separation theory, phases, equipment needed, ease of use, accuracy, sampling, and sampling techniques, automation, accuracy, and quantitation.

III. Gas Chromatography (GC) [USP <621>]

A. Objective

To present theory, instrumentation, parameters, and techniques for GC pharmaceutical analysis (topics outlined below). The student is expected to read and become familiar with the following techniques as described in the USP, other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory/Applications
  2. Instrument Components
    1. Columns
      1. Packed Columns
      2. Capillary Columns
    2. Gases
    3. Temperatures
      1. Isothermal
      2. Temperature Program
    4. Injection
      1. Packed
      2. Split/Splitless
    5. Detectors
      1. FID
      2. ECD
      3. Nitrogen/Phosphorus
      4. MS
      5. Other
    6. Data Handling
    7. Calculation Techniques 
  3. Sampling Techniques
    1. Direct Injection Techniques
    2. Autoinjection 
    3. Headspace Sampling
  4. Operation
  5. Quality Assurance (System Suitability)

B. Exercises

  1. For the following exercises use product 5. 'Acetaminophen Oral Suspension' identified in Appendix 1.
    • Alcohol Content  (if alcohol not already present  spike at a 5% concentration)  Method 2 <611>  [packed column GC analysis],  part 5.3
  2. For the following exercises use product 6. 'Caffeine (API)' identified in Appendix 1. Prepare a series of standards.
    • Organic volatile impurities (OVI) Method I <467>  [Capillary column GC analysis],  part 6.7
  3. Calculate the results using both area and peak height calculations (electronically or manually) and compare the results.

C.  Questions

  1. What type of products can be tested by GC? What products cannot be tested?  Describe a GC method that can analyze products that normally cannot be tested by a GC method.
  2. Describe how a Flame Ionization Detector (FID) works. Describe at least three other GC detectors commonly used. Which detector is similar to FID and how is it used?
  3. Describe capillary GC and how it differs from packed column GC. What are the advantages and disadvantages of each technique?  
  4. When is it appropriate to use temperature programming?  What are the advantages of using temperature programming. 
  5. GC commonly uses four different gases. Air, Nitrogen, Helium and Hydrogen. What is the purpose of each gas, how is it used and at what flow rates?
  6. (To be done at completion of each chromatography sections). Prepare a chart, comparing and relating each of the techniques used in chromatography for the following:  column materials, separation theory, phases, equipment needed, ease of use, accuracy, sampling, and sampling techniques, automation, accuracy, and quantitation.

IV. High Performance Liquid Chromatography (HPLC) [USP <621>]

A. Objective

To present theory, instrumentation, parameters, and techniques for HPLC pharmaceutical analyses (outline below). HPLC has become the most common and important analytical tool in the modern drug laboratory. The student is expected to read and become familiar with the following techniques as described in the USP or other literature, or through discussion with the trainer. The trainer is expected to provide explanations and devise simple exercises for the student to practice the techniques.

  1. Theory/Application 
  2. Instrument Components
    1. Columns
      1. Normal Phase Columns
      2. Reverse Phase Columns
      3. Ion Exchange Columns
      4. Guard Columns
      5. FAST Columns
      6. Specialty Columns
    2. Column Parameters
      1. Packings
      2. Size (both column and packing)
      3. Dimensions
    3. Mobile Solvents
      1. Aqueous and non-aqueous
      2. Buffers
      3. PIC and ion-pair modifiers
      4. Solvent Programming
    4. Injection
      1. Techniques
      2. Autoinjection
    5. Solvent Delivery (Pumps)
      1. Isocratic
      2. Solvent Program
    6. Detectors
      1. UV
      2. Electrochemical
      3. MS
      4. Other Specialty
    7. Data 
      1. Integration 
      2. Data Protection 
  3. Sampling Techniques
    • The need for clean samples and their preparation 
  4. Quality Assurance (System Suitability)

B. Exercises 

  1. For the following exercises use product 5. 'Acetaminophen Oral Suspensions' identified in Appendix 1.
    • Assay. MeOH/H2O,  Simple Isocratic systems,  part 5.4;
    • HPLC Identification Test B; and
    • pH <791> for product, parts 5.1 and 5.2. 
  2. For the following exercises use product 4. 'Acetaminophen and Caffeine Tablets' identified in Appendix 1.
    • Assay, HPLC multi-component with IS,  part 4.4,
    • HPLC Identification,  part 4.1, and
    • Dissolution and Uniformity of Dosage Units (HPLC),  parts 4.2 and 4.3. (optional) 
  3. For the following exercises use product 3. 'Aspirin Tablets' identified in Appendix 1.
    • Assay, HPLC ion-pair system,  part 3.5;
    • Limit of Free Salicylic Acid, HPLC,  part 3.4;
    • Uniformity of Dosage Units (HPLC), Identification test A & B, (optional); and
    • Identification tests A & B. (Dissolution done as part of Dissolution exercise).
  4. For the following exercises use product 9. 'Naltrexone Hydrochloride Tablets' identified in Appendix 1.
    • Assay, HPLC gradient system, part 9.4;
    • Identification,  part 9.1; and 
    • Optional - Uniformity of Dosage Units, part 9.3

C.  Questions

  1. Describe a typical 'basic' HPLC system and the purpose of each component.
  2. What is the difference between normal phase and reverse phase? List at least three column types for each phase.
  3. For the chromatograms obtained in exercise 2 'Acetaminophen and Caffeine Tablet' calculate the following for each of the peaks: Retention Time, Retention Volume, Relative Retention Time to IS, Capacity Factor, Resolution, Tailing, Theoretical Plates, Height Equivalent Theoretical Plate, Peak Widths at base, half height, and 5% height. Also calculate one set of sample results using both peak area and peak height calculations. Are the results different? If so, explain why differences may result.
  4. What is the purpose of the internal standard used in exercise 2? Calculate one set of sample results without using the internal standard.  Are the results different?  If so explain why differences may result. 
  5. When and why would gradient elution be used in HPLC? What is the affect of temperature on HPLC? Would temperature programming such as found in GC be effective for HPLC?
  6.  (To be done at completion of each chromatography sections). Prepare a chart, comparing and relating each of the techniques used in chromatography for the following:  column materials, separation theory, phases, equipment needed, ease of use, accuracy, sampling and sampling techniques, automation, accuracy, and quantitation.

3.4.2.4  Other Specialized Techniques

There are many specialized techniques used in pharmaceutical chemistry analysis. With the exception of dissolution, most of these techniques are unique to the specialty laboratory, or have not found wide recognition and thus are not usable for a basic training outline. All these techniques would be considered in advanced drug training. These other techniques will be mentioned by category only and could be expanded if the training laboratory has a need for this area of analytical techniques.  

I. Dissolution:   [USP <711>]

A. Objective

Dissolution is a technique commonly employed for tablet and capsule-type drug products. Modifications of the technique allow its use for other dosage forms such as patches, creams, and ointments. USP Apparatus 1 and 2 are covered in this section since these are the apparatus found in most drug laboratories.

  1. Theory
  2. Instrumentation
    1. USP Apparatus 1  (basket)
    2. USP Apparatus 2 (paddle)
    3. Other USP Apparatus (discussion only)
  3. Calibration
    1. Mechanical Calibration
      1. Temperature
      2. Rotation Speed
      3. Vibration
      4. Height (positioning)
      5. Wobble
      6. Centering
      7. Level
    2. USP Calibrators
      1. Dissolving (Prednisone)
      2. Non-dissolving (Salicylic Acid)
  4. Operation - Sampling
    1. Single Time period
    2. Profile Sampling
    3. Extended Release Products
  5. Autosampling Techniques

B. Exercises

  1. Calibrate an Apparatus 1 and an Apparatus 2 using the USP Prednisone and Salicylic Acid calibrator tablets.
  2. As part of the above calibration, perform a profile analysis for both prednisone and salicylic acid. Sample Prednisone at 15-minute intervals for 1 hour then 30-minute intervals for an additional two hours. Sample Salicylic Acid at 30-minute intervals for two hours and at hourly intervals for an additional four hours.
  3. For the following exercise use product #3. 'Aspirin Tablets' identified in Appendix 1.
    • Dissolution, Apparatus 1 @ 50-rpm --500ml pH 4.5 buffer - UV determination, part 3.3.
  4. For the following exercise use product #4. 'Acetaminophen and Caffeine Tablets' identified in Appendix 1.
    • Dissolution, Apparatus 2 @ 100-rpm - 900ml water - HPLC determination, part 4.2.
  5. For the following exercise use product #2. 'Ascorbic Acid Tablets' identified in Appendix 1.
    • Dissolution, Apparatus 2 @ 50rpm -900ml water 'Procedure for pooled sample' - titration determination,  Part 2.4.

C. Questions

  1. What parameters need to be checked and corrected before dissolution is run? Describe the effect that each would have on an analysis.
  2. What is the purpose of using two USP calibrators when checking a dissolution system?
  3. Exercise 2 demonstrates a profile analysis. When would this technique be used?  For what type of products could this technique be used? Find a monograph in USP that uses a profile type analysis.
  4. Describe the reason and procedure for removing air from the dissolution media. 
  5. Why not use water for all dissolution media and have constant paddle/basket rotation speed for all determinations?
  6. Compare in-vitro dissolution results with in-vivo clinical studies? Explain the answer. 

II.  Advanced Techniques

To be developed as advanced training on an as-needed basis:  (USP <___> identifies sections found in General Chapters, General Tests, and Assays found in the USP)

  1. Particle Size Analysis  (USP <786> )
  2. Capillary Electrophoresis (CE) (USP <727>)
  3. Ion Chromatography (USP <621>)
  4. Atomic Absorption Spectrophotometry (AA)     (USP <851> )
  5. Fluorimetry   (USP <851>)
  6. GC/Mass Spectrometry (USP <621> and <736> )
  7. LC/Mass Spectrometry (USP <621> and <736> )
  8. Nuclear Magnetic Resonance (NMR) (USP <761> )
  9. Refractive Index (USP <831> )
  10. Differential Scanning Calorimetry (DSC) and Thermal Gravimetric Analysis (TGA) (USP <891> )
  11. Polarographic Analysis (USP <801> )
  12. Electrophoresis (USP <726> )
  13. Immunoassays (USP <1045>)
  14. Tablet Friability (USP <1216> )
  15. Osmolarity (USP <785> )
  16. Dissolution Apparatus III to VIII (USP <711> and <724> )
  17. Drug Release (Extended Release and Delayed Release and Transdermal Systems) (USP <724>)
  18. Analytical Biotechnology using CE, HPLC, Isoelectric focusing. (USP <1047>)
  19. Aerosols, Metered-Dose Inhalers, and Dry Powder Inhalers (USP <601>)

3.4.3  Inspections/Investigations

All analysts are to participate in at least one inspection prior to attending the FDA sponsored FDA Law and Evidence Development Course. In addition, analysts in drug specialty laboratories are provided specialized training in the inspection of pharmaceutical laboratories as defined in Current Good Manufacturing Practices (cGMPs) under 21CFR Parts 210 and 211. This training program is developed according to the needs of the laboratory.  Analysts should become familiar with sections of the Investigations Operations Manual (IOM) that involve preparing for and conducting team inspections.  An example of training is as follows:

  1. Types of Inspections
    1. GMP
    2. Pre Approval
    3. Post Approval
    4. Contract Laboratory
    5. Private Laboratory (Import work)
    6. Clinical Laboratory
    7. Foreign Inspections
  2. Preparing for Team Inspections
  3. How to start an inspection (482)
  4. What to look for in the Laboratory
    1.  FDA Inspection Guides
  5. Evidence Development
    1. Documentation and affidavits
    2. Photography
  6. Prepare a 483
  7. Prepare an EIR

 

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