essay

• In-process control


  To check consistency of the product and prevent the production of sub-standard drug product by early detection of deviation
• Benefits of in-process control


  • Identifying problems early
  • Saving time & money
  • Reducing waste
  • Correcting product variations before the product reaches its final form
• In-process control activities


  1. Sampling

  2. Testing

  3. Inspection after every significant stage of the manufacturing process
• Purpose of sampling for in-process materials

  To ensure a good distribution of active ingredient and dosage strength
• Tests conducted during in-process testing

  • Identity
  • Strength
  • Purity
  • Quality as appropriate
• In-process control tests for tablets

  • Moisture content determination
  • Sieve (screen analysis) to determine particle size distribution
• Purpose of Disintegration Test (DT) for tablets

  To ensure that all of the tablets tested disintegrate completely after 15 minutes
• Requirement for friability test for compressed tablets

  It should not be more than 1.0%
• Purpose of hardness test for compressed tablets

  To measure the degree of force required to break a tablet
• Purpose of clarity and completeness of solution test for syrups/liquid preparations


  To ensure the solution is clear and complete as per product specifications
• Requirement for disintegration time (DT) test for capsules


  To determine the disintegration time, which should meet specific requirements
• Factors to consider when determining frequency of sampling and testing

  • Precision of machine
  • Speed of the process
  • Batch size
• How tolerance limits and in-process material specifications should be derived


  From the best result obtained from previous acceptable batches and consistent with finished product specifications
• What should be considered in determining realistic specification limits


  Experimental results obtained for the mean and standard deviation
• Why In-Process Control is important

  To ensure batch uniformity and integrity of the product
• What should be included in finished product specifications

  • The designated name of the product and the code reference where applicable
  • The formula
  • A description of the pharmaceutical form and package details
  • Directions for sampling and testing
  • The qualitative and quantitative requirements, with the acceptance limits
  • The storage conditions and any special handling precautions, where applicable
  • The shelf-life
• What the monograph USP NF FPS aims to provide

  An overview of the analytical testing performed to release a medicinal product for clinical or commercial use, and specifications that ensure the quality and performance of the released medicinal product
• Responsibility of a pharmaceutical manufacturer

  To ensure the quality, purity, identity, and strength of each lot of drug product manufactured
• What specifications are defined as

  Critical quality standards, a document that includes a list of tests, references to analytical procedures, and appropriate acceptance criteria (numerical range or limit)
• What 'conforms to specification' means

  It means that the drug product, when tested to the analytical procedures, will meet the listed acceptance criteria
• Different categories of specifications based on intended use

  • Release testing
  • Stability testing
• What is included in a specification sample

  Compendia
• What the United States Pharmacopeial Convention is responsible for

  Setting standards for quality, purity, identity, and strengths of medicines, food ingredients, and dietary supplements
• How often the European Pharmacopeia Commission is published

  Every three years with supplements
• Purpose of a monograph according to USP

  To describe an article (e.g. drug substance, drug product, excipient, compounded preparation) and provide information on tests needed to ensure the substance is of appropriate identity, strength, quality, and purity
• Purpose of release testing

  To check the quality of the substance or preparations prior to using or distribution for consumption
• Classifications of testing based on the nature of testing performance

  • Chemical test
  • Physical test
  • Microbiological test
• Examples of tests used in stability testing

  • Microbial tests
  • Degradation product tests
• Classifications of testing based on the attribute being tested

  • General quality attributes
  • Product performance
• Examples of tests under the identity test based on general test classification

  • Physical method
  • Chemical method
  • Instrumental method
• Purpose of the assay test

  To determine the strength or content of the API in the dosage form
• Definition of an impurity in a drug product


  Any component that is not the API or an excipient
• What residual solvents are in the context of impurities in drug products

  Organic volatile chemicals used or produced in the manufacture of drug substances, excipients, or preparation of drug products where an organic solvent is used during the manufacture
• Five general types of injectable presentations


  • Drug injection
  • Drug for injection
  • Drug injectable emulsion
  • Drug injectable suspension
  • Drug for injectable suspension
• Specific tests for drug injection

  • Universal tests
  • pH
  • Particulate matter
  • Sterility
  • Leakers test
  • Clarity
  • Bacterial endotoxins test
  • Uniformity of dosage forms
  • Pyrogen test
  • Turbidimetric techniques
  • Chromogenic technique
• Purpose of the pyrogen test for drug injection

  To detect dead lipopolysaccharide from gram-negative bacteria, which can still cause fever
• Specific tests for immediate-release tablets

  • Universal tests
  • Uniformity of dosage form
  • Tablet friability
  • Tablet breaking force
• Purpose of water determination for immediate-release tablets


  Karl Fischer or LOD
• Purpose of tablet friability test for immediate-release tablets

  To ensure that the tablet will not break or chip during coating, packaging, or distribution
• Purpose of tablet breaking force test for immediate-release tablets

  To ensure proper control during manufacturing, which can affect in-vitro and in-vivo product performance