QC 1

• Pharmaceutical regulations and GMP requirements were created and put in place as responses to tragic circumstances and to prevent future tragedies
• These circumstances can be called as the milestones for the evolution of quality aspects in the pharmaceuticals
• Children who received antitoxin for diphtheria treatment died of tetanus because the horse serum that had been used to prepare the antitoxin was contaminated with tetanus

  1901
• Syrup to calm "colicky" babies and "tonics" for adults often contained alcohol, opium, or morphine, which addicted many people who used them
• Pure Food and Drug Act - First Act required selected dangerous ingredients to be labeled on all drugs


  1906
• The wrong raw material and an elixir of sulfanilamide, anti-infective drug used in 1935. One company used diethylene glycol, a poisonous solvent and chemical analog of antifreeze, in an oral "elixir of sulfanilamide." Before the problem was discovered, 107 people died, many of them children


  1930s
• Congress passed the Federal Food, Drug and Cosmetic (FD&C) Act. For the first time, companies were required to prove that their products were safe before marketing them


  1938
• Nearly 300 people were harmed (some of them died) by one company's sulfathiazole tablets, a sulfa drug tainted with the sedative Phenobarbital


  1941
• That incident caused FDA to drastically revise manufacturing and quality control requirements, leading to what would later be called GMPs
• Thalidomide was marketed in Europe as a sleeping pill and to treat morning sickness. When regulatory agencies gave permission to sell the drug for that indication, they had no knowledge of its serious side effects. It turned out to be teratogenic, It caused serious deformities in developing fetuses


  1960s
• Manufacturers must prove efficacy of products before marketing them and ensure stricter control over drug testing
• Children whose mothers took thalidomide in the first trimester were born with severely deformed arms and legs. An estimated 10,000 cases of infant deformities in Europe were linked to thalidomide use
• The 1972 Devonport, UK, incident resulted in at least five deaths when drug products designed to be sterile became contaminated and recipients developed infections. An unwritten change to autoclave operation, communicated orally between operators, resulted in dextrose IV solutions that were not uniformly sterile


  1970s
• GMPs for drugs (21 CFR Parts 210 and 211) and medical devices (21 CFR 820) were made final. They were intended to help ensure the safety and efficacy of all products

  1978
• 12-year-old Mary Keller man died after taking an extra-strength Tylenol acetaminophen capsule, Six other people died after taking the same drug. Johnson & Johnson announced a nationwide recall of 31 million bottles of Tylenol. The investigation revealed that a criminal tamper had opened up and laced some capsules with cyanide


  1982
• Congress passed the Federal Anti-Tampering Act, making it a crime to tamper with packaged consumer products


  1983
• An outbreak of toxic reactions to over-the-counter tryptophan, a dietary supplement, resulted in 38 deaths and probably thousands of less severe reactions. The event was the result of a manufacturing process change that increased the level of a harmful byproduct. Doses that had previously been safe now caused toxicity

  1989
• The Regulatory Authorities all over the world have accepted that a pharmaceutical product which meets the following five characteristics can be expected as a quality product: Identity, Strength, Safety, Purity, Efficacy
• Quality Assurance


  Obtaining confidence that, required quality of product or service is satisfactory for their intended use
• Quality Assurance


  • QA is a managerial tool
  • QA is the totality of the arrangement made with the objectives of ensuring that pharmaceutical products are of quality required for intended use
• Functions of QA in Pharmaceutical industry


  • To ensure raw materials used in the manufacturing are approved and procured from approved vendor
  • To ensure all data's are recorded as per cGMP and is reviewed for accuracy and traceability
  • To ensure procedures are in place for performing the activities, operating and calibrating the equipment
  • To ensure quality is built up in the plant, process, product and that a Robust Quality system is in place
  • To prepare and approve Quality Policy, Quality Objectives, Quality Manual and Validation Master Plan
  • To periodically monitor the Quality Objectives
  • To monitor all validation & stability activities are completed as per the schedule
  • To ensure that all changes impacting the product and the established systems are documented and reviewed to analyze the impact
  • To conduct trainings like induction, On job, Scheduled and after any changes to respective individuals on time
  • To ensure that all deviations & Market complaints are logged, investigated to identify the root cause so as to take prevent recurrence
  • To prepare Annual product quality reports, trending of data, determining product and process performance
  • To arrange and conduct the self inspection
  • To review of related batch manufacturing records and QC testing data Prior to release of any batch
• Quality Control


  Part of GMP concerned with sampling, testing and specifications. QC is a corrective tool
• Functions of QC in pharmaceutical industry

  • Preparation of specifications for testing of materials and products
  • Carrying out Sampling and testing of materials or products
  • Environment Monitoring
  • Conducting stability studies
  • Investigating test failures
  • Analytical method validation
  • Evaluation of complaint samples
• Scope of QC in pharmaceutical

  • To identify defects in the finished product
  • To identify defects after a product is developed and before it's released
  • Finding sources of quality problems to continually meet customer's requirement
  • Analytical techniques used to maintain the product quality and process
• Quality Assurance Vs Quality control

  • QA is Process oriented, QA aims at defect prevention, QA goal is to improve the process development so that the defect don't rise, QA is company based
  • QC is product oriented, QC aims at defect identification, QC goal is to improve the final product by identifying defects, QC is laboratory based
• Pharmacopoeia


  A legal and official book issued by recognized authorities usually appointed by Government of each country, comprising list of pharmaceutical substances, formulae along with their description and standards

  
• Monographs

  Descriptions of preparations in a pharmacopoeia

  
• List of Pharmacopoeias

  • British
  • European
  • Indian
  • International
  • United States
• British Pharmacopoeia (BP)

  • First edition published in 1864
  • Consists of two sections: Part I - Materia Medica, Part II - Preparation & compounds
  • Titles of drugs & preparations in English instead of Latin and metric system from 8th edition published in 1953
  • Published annually
• British Pharmacopoeia (BP) 2007-2009

  • Given in Six Volumes: Volume I & II contains medicinal substances, Volume III contains formulated preparations, blood related products, immunological products, radiopharmaceutical preparations, surgical materials & homoeopathic preparations, Volume IV contains supplementary chapters, IR spectra etc., Volume V contains veterinary, Volume VI contains CD ROM version

  
• United States Pharmacopoeia (USP)

  • First edition published on 15th December 1820 in both Latin & English
  • Published at Ten years intervals from 1820 to 1942
  • Published at Five years intervals from 1942 to 2000
  • Published annually from 2002

  
• European Pharmacopoeia (EP)

  • European pharmacopeia commission started working since 1964
  • 1st edition published in 1967, 2nd edition in 1980, 3rd edition in 1997, 4th edition in 2001, 5th edition in 2004, 6th edition in 2007, 7th edition in 2010, 8th edition in 2013
• Monographs

  • Based on the specifications for substances used in medicinal products approved in Member States
  • Interested parties should be invited to participate in the elaboration of the monograph before publication
• Preparation of a monograph

  1. Gather information on the substance: origin, whether mixture or single entity, method of preparation, different crystalline forms, enantiomers, hydrates, different entities (acid, base, salt, etc)

  2. Consult existing monographs on similar substances

  3. Use the International Nonproprietary Name (INN) established by the World Health Organization in the title

  4. Ascertain the chemical structure precisely to establish the exact graphic formula, empirical formula, relative molecular mass, chemical name

  5. Specify the content and assay limits

  6. Describe the appearance, solubility, stability factors, hygroscopicity, solid-state properties, other characteristics, behavior in solution

  
• Identification

  Provide confirmation of the identity of the substance through physical and/or chemical tests and reactions
• Tests

  Appearance of solution: to ascertain the general purity of a substance by the detection of impurities insoluble in the solvent or of coloured impurities