Validation in the Pharmaceutical and Medical Industry

• FDA stands for Food and Drug Administration
• API stands for Active Pharmaceutical Ingredient
• cGMP stands for current good manufacturing practice
• GEP stands for good engineering practice
• LVP stands for Linear Process Validation
• PPM stands for Policy and Procedure Manual
• IQ stands for Installation Qualification
• OQ stands for operative qualification
• PQ stands for performance qualification
• IMP stands for investigate medical product
• SOP stands for standard operating procedure
• A PharmaChemical Ireland (PCI) working group is a group that consists of representatives from PCI members (companies) and where relevant representatives from other appropriate groups/agencies
• Validation is the means of ensuring and providing DOCUMENTED EVIDENCE that facilities, utilities, systems, equipment, and processes are capable of repeatedly and reliably producing a finished product of the required quality.
• GMP is defined as: “That part of Quality Assurance which ensures that products are produced and controlled to the quality standards appropriate to their intended use.”
• GMP includes:

  • record-keeping
  • personnel qualifications
  • sanitation
  • cleanliness
  • equipment verification
  • process validation
  • complaint handling
• Validation is a legal requirement
• Validation is important as in-process/ finished testing is inadequate
• In 1938 the Food, Drug and Cosmetic Act was signed in the US
• Pharmaceutical Regulation Kefauver-Harris Amendments 1962 required that:

  • not only were drugs safe but they also worked for their intended use
  • animal trials were necessary
  • investigators were responsible for supervising drugs under study
  • manufacturers had to inform patients that the drugs were used for investigational purposes and get the patient's consent
  • a demonstration that the drug worked before it went on the market
  • manufacturers had to report unexpected harm
  • FDA had authority over marketing
• GMP in the USA was finalized in 1978
• GMP was finalized in the US in 1979
• In 1864 the British Pharmacopoeia was produced it aimed to standardise testing and preparation of medicines
• In Ireland in 1875 The Pharmacy Act gave pharmaceutical chemistry a monopoly on the sale of ‘statutory poisons’
• In 1931 Pharmacopoeias Act made the standards of the BP apply to drugs or preparations sold in Ireland
• In 1934 in IrelandThe Dangerous Drug Act limited the sale of specific medicines to prescription. Applied mainly to narcotics, opium, morphine and cocaine
• The Pharmaceutical Society of Great Britain was established in 1841
• In Great Britain, in 1868 The Pharmacy Act was enacted
• Up until 1966, in the EU any individual could have made any drug so long as it complied with the pharmacopoeia
• In 1966 the National Drugs Advisory Board (NDAB) was made in Ireland, it held no authority and its function was:

  • assessing the safety of drugs
  • licensing the manufacture, importation, distribution, and the sale of drugs
  • Obtaining and assessing information on the adverse effects of drugs
  • registration and inspection of premises of drug manufactures
• In 1995 the Irish Medicines Board was set up to regulate the sale of medicines in Ireland, and they issued various licences such as:

  • licencing of medical products for human use
  • licencing of veterinary products
  • licencing of wholesalers of human medicines
  • licensing of manufacturers of human and veterinary medications
  • licensing of clinical trials
• The first and basic EEC Directive to control medicines was introduced in 1965
• Directive75/319/EEC)

  • Set up the committee for Proprietary Medicinal Products (CPMP) to assist member states in reaching agreed decisions on medicines licensing control matters
  • Established principle that manufacturers are subject to inspection
  • Manufacturer cannot produce without manufacturing licence granted by a relevant authority
  • Manufacturing must take place in accordance with principles and guidelines of Good Manufacturing Practice as laid down by the law
  • Manufacture must be supervised by QP
  • QP must certify batches
• In 1971, in the UK GMP 'the orange guide' was published. This document stated that:

  • Procedures should be periodically reviewed to ensure they continue to be effective
  • • Procedures should undergo a regular critical appraisal to ensure that they are, and remain capable of achieving the results they were intended to achieve
  • Note that the word validation is not used
• The UK GMP Guide was amended in 1974 to include the following:

  • Sterilisation methods should be proven under conditions of use and checked at regular intervals.
  • The efficacy of aseptic processes (performed under sterile conditions) should be confirmed by media simulation.
  • Manufacturers replace starting materials with microbial growth media and run it through the process-(running a blank).
• In 1977 the GMP Guide in the UK was amended to include the following:

  • Equipment should be shown to be capable of carrying out the process for which is used.
  • Weighing and measuring equipment should be regularly checked and verified.
  • Manufacturing processes should also be evaluated.
  • Cleaning procedures of known effectiveness should be used.
• In 1983 the UK GMP guide added:

  • computer systems
  • analytical methods
  • documentation
• The orange guide was superseded by the EU version, the Eudralex
• Volume One of the Eudralex - EU pharmaceutical legislation for medicinal products for human use.
• Volume Two - notice to applicants and regulatory guidelines for medicinal products for human use
• Volume Three - scientific guidelines for medicinal products for human use