QUALIFICATION AND VALIDATION PROTOCOLS

• Qualification and validation protocols


  Describe the qualification and validation study to be performed, including significant background information, objectives, site, responsible personnel, SOPs, equipment, standards and criteria, type of validation, processes and/or parameters, sampling, testing and monitoring requirements, and predetermined acceptance criteria
• The protocol should be approved prior to use and any changes should be approved prior to implementation
• There should be a description of how the results will be analysed
• Standards


  The 'yardstick of quality' which is set through local standards like EN, BS, DIN, and the international ISO model
• Examples of ISO, EU, and UK standards relevant to pharmaceutical manufacture and clinical trials


  • ISO-9000
  • ISO-9001
  • ISO-9002
  • ISO-9003
  • ISO-9004
  • ISO-10012-1
  • Schedules 1 and 2 of the Medicines for Human Use (Clinical Trials) Regulations (UK), 2004
  • CPMP ICH/135/95 – ICH Topic (E6, section 6.4.9) (R1) – Guideline for Good Clinical Practice (2002)
• A quote from Deming: 'Cheaper is not always better BUT better is always cheaper'
• Chiral properties


  A large proportion of NCEs will have one or more chiral centres, and only single enantiomers can be used nowadays as different enantiomers produce different pharmacological responses
• Packaging and labeling control


  Detailed written procedures for receipt, identification, storage, handling, sampling, examination, and/or testing of labeling and packaging materials; separate storage of labels and labeling materials; prevention of mix-ups and cross-contamination; identification of drug products with lot or control numbers; examination of packaging and labeling materials before use; inspection of packaging and labeling facility before use
• Issuance of labeling


  Strict control over issuance of labeling; examination of labeling materials for identity and conformity; reconciliation of quantities of labeling issued, used, destroyed, and returned; destruction of excess labeling; written procedures for control of labeling issuance
• Expiration dating


  All packaged drug products must carry an expiration date determined from stability testing; expiration dates must be related to recommended storage conditions; expiration information required for reconstituted and unreconstituted forms
• Documentation required in batch production records


  • Dates
  • Identity of major equipment used
  • Identification of components and in-process materials
  • Weights and measures of components
  • In-process and laboratory control results
  • Inspection of packaging and labeling area
  • Actual yield and percentage of theoretical yield
  • Labeling control records
  • Description of containers and closures
  • Sampling performed
• Quality control guidance


  Describes a quality systems model with four major factors: management responsibilities, resources, manufacturing operations, and evaluation; covers elements like facilities and equipment, outsourced operations, design and development, nonconformities, data analysis, audits, risk management, corrective and preventive action, and improvement
• Bioequivalence


  Chemical equivalents which, when administered to the same individuals in the same dosage regimen, will result in comparable bioavailability