A summary of GMPs from the original "bread laws" to today

1. GMPs - History and the 2008 Revisions What does GMP mean to me? Frank Settineri Veracorp LLC [email_address] 908-499-5540

3. GMPs - History and the 2008 Revisions What does GMP mean to me? What is a GMP? Good Manufacturing Practice or GMP current Good Manufacturing Practice or cGMP

4. GMPs - History and the 2008 Revisions What does GMP mean to me? What is a GMP? Recognized worldwide for the control and management of manufacturing and testing of foods, pharmaceuticals, medical devices http://en.wikipedia.org/wiki/Current_good_manufacturing_practice

5. GMPs - History and the 2008 Revisions What does GMP mean to me? What is a GMP? In the US, "current good manufacturing practice" appears in 501(B) of the 1938 Food, Drug, and Cosmetic Act (21USC351)

6. GMPs - History and the 2008 Revisions What does GMP mean to me? What is a GMP? US courts may decide that a drug product is adulterated even if there is no specific regulatory requirement that was violated

7. GMPs - History and the 2008 Revisions What does GMP mean to me? What is a GMP? Today GMPs mean a process must be performed according to industry standards

8. GMPs - History and the 2008 Revisions What does GMP mean to me? What is a GMP? Requirements will apply to all manufactures of dietary supplements by June, 2010 http://www.fda.gov/bbs/topics/NEWS/2007/NEW01657.html

10. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

11. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1202 King John of England proclaimed the first English food law, Assize of Bread

12. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1202 Assize of Bread prohibited adulteration of bread with ingredients such as ground peas or beans

13. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1820 USP was established Eleven physicians in Washington First compendium of standard drugs for US

14. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1848 Drug Importation Act Requires U.S. Customs Service to stop entry of adulterated drugs from overseas

15. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1862 President Lincoln appoints a chemist, Charles M. Wetherill, to serve in new Department of Agriculture Beginning of Bureau of Chemistry, the predecessor of the Food and Drug Administration

16. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1883 Dr. Harvey Wiley becomes chief chemist of Bureau of Chemistry's food adulteration studies

17. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Dr. Wiley called the "Crusading Chemist" and "Father of the Pure Food and Drugs Act." Retired from government in 1912 and died in 1930

18. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1897 Tea Importation Act passed Customs inspection of all tea entering U.S. ports, at the expense of the importers

19. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1898 Association of Official Agricultural Chemists ( AOAC International) establishes Committee on Food Standards headed by Dr. Wiley

20. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1902 The Biologics Control Act is passed to ensure purity and safety of serums, vaccines, and similar products used to prevent or treat diseases in humans

21. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1902 Congress appropriates $5,000 to study chemical preservatives and colors and their effects on digestion and health

22. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1902 Dr. Wiley's studies draw widespread attention to the problem of food adulteration Public support for passage of a federal food and drug law grows

23. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

24. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Despite these laws, there was a cavalier attitude regarding drugs and medicines

25. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Chemical preservatives and toxic colors were virtually uncontrolled

26. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Sanitation was primitive Ice was principal means of refrigeration

27. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Milk was unpasteurized and cows were not tested for tuberculosis

28. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Pioneers of bacteriology were just starting their string of victories over infectious diseases

29. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Thousands of so-called ‘patent’ medicines such as ‘ Kick-a-poo Indian Sagwa ’ and ‘ Warner's Safe Cure for Diabetes ’ were available

30. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Jamba Juice?

31. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Medicines containing opium, morphine, heroin, and cocaine were sold without restriction and their labels gave no hint of their presence

32. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Saw Palmetto? Ephedrine?

33. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? I lost twenty pounds by eating cookies!

34. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Labels did not list ingredients and warnings against misuse were nonexistent The information the public received came frequently from bitter experience

35. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Steve Warshak, founder of Berkeley Premium Nutraceuticals, sentenced to 25 years in prison Charged with deceptive ads for Enzyte, a sexual performance product

36. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Also found guilty for an automatic credit card charging scheme that took money from customers without letting them return or cancel orders

37. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Medicine men competed with the circuses , the minstrel shows, and "wild west" performers to entertain the public – and to sell their products

38. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Hamlin's Wizard Oil was one of the most popular and spectacular drugs of the big touring medicine shows This liniment (for minor aches and pains) was sold long after the shows had eased

39. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Snake oil?

40. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Shocking disclosures of insanitary conditions in meat-packing plants, use of poisonous preservatives and dyes, and cure-all claims for worthless and dangerous patent medicines

41. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

42. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1906 Spurred by Dr. Wiley’s efforts, the Food and Drugs Act was passed on June 30 Signed by President Theodore Roosevelt

43. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1906 Interstate commerce of misbranded and adulterated foods, drinks and drugs was p rohibited

44. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Food adulteration continued to flourish because judges could find no specific authority for the standards of purity and content

45. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Such products as " fruit" jams made with water, glucose, grass seed, and artificial color undercut the market for honest products

46. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Today’s Gatorade?

47. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1906 The Meat Inspection Act is passed the same day

48. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1907 First Certified Color Regulations, requested by manufacturers and users, list seven colors found suitable for use in foods

49. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1911 In U.S. vs Johnson, Supreme Court rules that 1906 Food and Drugs Act does not prohibit false therapeutic claims but only false and misleading statements about the ingredients or identity of a drug

50. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1911 Science + Politics = Disaster

51. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1912 Congress enacts Sherley Amendment to reverse Johnson ruling Prohibits labeling medicines with false therapeutic claims Difficult to prove

52. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Cavalier attitude remained

53. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1933 FDA recommends complete revision of 1906 Food and Drugs Act. Bill introduced into Senate, launching a five-year legislative battle

54. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1937 Elixir of Sulfanilamide, containing diethylene glycol, kills 107 persons , many of whom are children

55. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

56. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Precipitates Federal Food, Drug, and Cosmetic (FDC) Act

57. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1938 The Federal Food, Drug, and Cosmetic (FDC) Act of 1938 passed by Congress

60. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1944 Public Health Service Act passed Regulated biologicals and control of communicable diseases

62. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1949 FDA publishes first guidance to industry "Procedures for the Appraisal of the Toxicity of Chemicals in Food" Known as the " black book "

63. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1953 Factory Inspection Amendment requires FDA to give manufacturers written reports of conditions observed during inspections and analyses of factory samples

64. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1962 Thalidomide found to cause birth defects in thousands of babies born in western Europe Aroused public support for stronger drug regulation

65. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

66. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1962 Drug Amendments Congress instructed FDA to require that all drugs be produced according to Good Manufacturing Practices

67. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? The word “ current ” was later added to make it “cGMP” to imply that the regulation allows for changing technology in attaining GMPs

68. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1973 US Supreme Court upholds 1962 drug effectiveness law and endorses FDA to control products by regulations rather than litigation

69. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1978 cGMPs were rewritten to deal with personnel and facilities, processes and products

70. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1988 FDA officially established as an agency of the Department of Health and Human Services Commissioner officially appointed by the President

71. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

72. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Judge Wolin Barr Laboratories http://www.gmp1st.com/barrsum.htm

75. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Laboratory investigation consists of more than a retest Inability to identify an error's cause affects retesting procedures, not the investigation inquiry

77. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Barr Decision raised the “bar” (sic)

78. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? 1997 FDA Modernization Act Required consistent and efficient regulatory requirements

80. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

81. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? These newer laws, partially provoked by political pressure, have been designed to provide safer, risk-free medicines

82. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? They may unintentionally raise development costs and obliterate research programs

83. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations have evolved from simple, low impact rules to complicated, daunting guidelines

84. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Provided the impetus for individuals to subvert the production of safe and effective drugs in favor of creating all types of redundant documents, SOPs and policies

85. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? The lesson?

86. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Do the right thing

87. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? GMPs continue to evolve, partially due to mistakes and partially based on companies wanting more guidance

88. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

90. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs 21 CFR Part 211 Organization Buildings and Facilities Equipment Control of Components Production and Process Controls Packaging and Labeling Holding and Distribution Laboratory Controls Records and Reports Returned and Salvaged Goods

91. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart A - General Provisions 211.1 - Scope. 211.3 - Definitions. Subpart B - Organization and Personnel 211.22 - Responsibilities of quality control unit. 211.25 - Personnel qualifications. 211.28 - Personnel responsibilities. 211.34 - Consultants.

92. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart C - Buildings and Facilities 211.42 - Design and construction features. 211.44 - Lighting. 211.46 - Ventilation, air filtration, air heating and cooling. 211.48 - Plumbing. 211.50 - Sewage and refuse. 211.52 - Washing and toilet facilities. 211.56 - Sanitation. 211.58 - Maintenance

93. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart D – Equipment 211.63 - Equipment design, size, and location. 211.65 - Equipment construction. 211.67 - Equipment cleaning and maintenance. 211.68 - Automatic, mechanical, and electronic equipment. 211.72 - Filters.

94. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart E - Control of Components and Drug Product Containers and Closures 211.80 - General requirements. 211.82 - Receipt and storage of untested components, drug product containers, and closures. 211.84 - Testing and approval or rejection of components, drug product containers, and closures. 211.86 - Use of approved components, drug product containers, and closures. 211.87 - Retesting of approved components, drug product containers, and closures. 211.89 - Rejected components, drug product containers, and closures. 211.94 - Drug product containers and closures .

95. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart F - Production and Process Controls 211.100 - Written procedures; deviations. 211.101 - Charge-in of components. 211.103 - Calculation of yield. 211.105 - Equipment identification. 211.110 - Sampling and testing of in-process materials and drug products. 211.111 - Time limitations on production. 211.113 - Control of microbiological contamination. 211.115 - Reprocessing.

96. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart G - Packaging and Labeling Control 211.122 - Materials examination and usage criteria. 211.125 - Labeling issuance. 211.130 - Packaging and labeling operations. 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products 211.134 - Drug product inspection. 211.137 - Expiration dating.

97. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart H - Holding and Distribution 211.142 - Warehousing procedures. 211.150 - Distribution procedures. Subpart I - Laboratory Controls 211.160 - General requirements. 211.165 - Testing and release for distribution. 211.166 - Stability testing. 211.167 - Special testing requirements. 211.170 - Reserve samples. 211.173 - Laboratory animals. 211.176 - Penicillin contamination.

98. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart J - Records and Reports 211.180 - General requirements. 211.182 - Equipment cleaning and use log. 211.184 - Component, drug product container, closure, and labeling records. 211.186 - Master production and control records. 211.188 - Batch production and control records. 211.192 - Production record review. 211.194 - Laboratory records. 211.196 - Distribution records. 211.198 - Complaint files.

99. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Subpart K Returned and Salvaged Drug Products 211.204 - Returned drug products. 211.208 - Drug product salvaging.

100. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs These are the GMPs we all love We’ve all lived with them

101. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs What do they really mean?

102. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs 1. People 2. Facilities 3. Integrity

106. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs Use common sense That’s all you need to do

107. GMPs - History and the 2008 Revisions What does GMP mean to me? Current GMPs GMPs are not complicated if you do what is right

108. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

110. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions Summary related to microbiology All changes, and a summary of the reasoning behind them are available at http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-20709.pdf (Federal Register / Vol. 73, No. 174 / Monday, September 8, 2008 /Rules and Regulations pp. 51919-51933) http://www.microbiologyforum.org/PMFNews/PMFNews.14.12.0812.pdf

111. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.67 Equipment cleaning and maintenance. (a) Equipment and utensils shall be cleaned, maintained, and as appropriate for the nature of the drug, sanitized and/or sterilized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements

112. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.68 Automatic, mechanical, and electronic equipment (c) Such automated equipment used for performance of operations addressed by §§ 211.101(c) or (d), 211.103, 211.182, or 211.188(b)(11) can satisfy the requirements included in those sections relating to the performance of an operation by one person and checking by another person if such equipment is used in conformity with this section, and one person checks that the equipment properly performed the operation.

113. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.72 Filters Filters for liquid filtration used in the manufacture, processing, or packing of injectable drug products intended for human use shall not release fibers into such products. [Fiber-releasing filters may not be used in the manufacture, processing, or packing of these injectable drug products unless it] Fiber-releasing filters may be used when it is not possible to manufacture such drug products without the use of such filters. If use of a fiber releasing filter is necessary, an additional nonfiber-releasing filter having a maximum nominal pore size rating of 0.22 micron (0.45 micron if the manufacturing conditions so dictate) shall subsequently be used to reduce the content of particles in the injectable drug product. The use of an asbestos containing filter is prohibited.

114. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.82 Receipt and storage of untested components, drug product containers, and closure (b) Components, drug product containers, and closures shall be stored under quarantine until they have been tested or examined, whichever is as appropriate, and released. Storage within the area shall conform to the requirements of weighing, measuring, or subdividing operations are performed by automated equipment under §211.68, only one person is needed to assure paragraphs (c)(1), (c)(2), and (c)(3) of this section. (d) Each component shall either be added to the batch by one person and verified by a second person or, if the components are added by automated equipment under § 211.68, only verified by one person.

115. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.84 Testing and approval or rejection of components, drug product containers, and closures (c) Samples shall be collected in accordance with the following procedures: (1) The containers of components selected shall be cleaned [where necessary, by appropriate means] when necessary in a manner to prevent introduction of contaminants into the component

116. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.84 Testing and approval or rejection of components, drug product containers, and closures (d) Samples shall be examined and tested as follows: (3) Containers and closures shall be tested for conformance with all appropriate written [procedures] specifications. In lieu of such testing by the manufacturer, a certificate of testing may be accepted from the supplier, provided that at least a visual identification is conducted on such containers/closures by the manufacturer and provided that the manufacturer establishes the reliability of the supplier's test results through appropriate validation of the supplier's test results at appropriate intervals.

117. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.84 Testing and approval or rejection of components, drug product containers, and closures (6) Each lot of a component, drug product container, or closure [that is liable to] with potential for microbiological contamination that is objectionable in view of its intended use shall be subjected to microbiological tests before use.

118. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.94 Drug product containers and closures (c) Drug product containers and closures shall be clean and, where indicated by the nature of the drug, sterilized and processed to remove pyrogenic properties to assure that they are suitable for their intended use. Such depyrogenation processes shall be validated.

119. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.101 Charge-in of components (c) (3) The containers are properly identified. If the weighing, measuring, or subdividing operations are performed by automated equipment under § 211.68, only one person is needed to assure paragraphs (c)(1), (c)(2), and (c)(3) of this section. (d) Each component shall either be added to the batch by one person and verified by a second person or, if the components are added by automated equipment under § 211.68, only verified by one person.

120. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.103 Calculation of yield Actual yields and percentages of theoretical yield shall be determined at the conclusion of each appropriate phase of manufacturing, processing, packaging, or holding of the drug product. Such calculations shall either be performed by one person and independently verified by a second person, or, if the yield is calculated by automated equipment under § 211.68, be independently verified by one person.

121. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.110 Sampling and testing of in-process materials and drug products (a) To assure batch uniformity and integrity of drug products, written procedures shall be established and followed that describe the in-process controls, and tests, or examinations to be conducted on appropriate samples of in-process materials of each batch. Such control procedures shall be established to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product.

122. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.110 Sampling and testing of in-process materials and drug products Such control procedures shall include, but are not limited to, the following, where appropriate: (1) Tablet or capsule weight variation; (2) Disintegration time; (3) Adequacy of mixing to assure uniformity and homogeneity; (4) Dissolution time and rate; (5) Clarity, completeness, or pH of solutions. (6) Bioburden Testing

123. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.113 Control of microbiological contamination (a) Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required to be sterile, shall be established and followed. (b) Appropriate written procedures, designed to prevent microbiological contamination of drug products pur- porting to be sterile, shall be established and followed. Such procedures shall include validation of all aseptic and any sterilization processes.

124. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.160 General requirements (b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity. Laboratory controls shall include: (Continued…)

125. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.160 General requirements (1) Determination of conformanity [ce] to appropriate written specifications for the acceptance of each lot within each shipment of components, drug product containers, closures, and labeling used in the manufacture, processing, packing, or holding of drug products. The specifications shall include a description of the sampling and testing procedures used. Samples shall be representative and adequately identified. Such procedures shall also require appropriate retesting of any component, drug product container, or closure that is subject to deterioration.

126. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.182 Equipment cleaning and use log A written record of major equipment cleaning, maintenance (except routine maintenance such as lubrication and adjustments), and use shall be included in individual equipment logs that show the date, time, product, and lot number of each batch processed. If equipment is dedicated to manufacture of one product, then individual equipment logs are not required, provided that lots or batches of such product follow in numerical order and are manufactured in numerical sequence.

127. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.182 Equipment cleaning and use log In cases where dedicated equipment is employed, the records of cleaning, maintenance, and use shall be part of the batch record. The persons performing and double-checking the cleaning and maintenance (or, if the cleaning and maintenance is performed using automated equipment under § 211.68, just the person verifying the cleaning and maintenance done by the automated equipment) shall date and sign or initial the log indicating that the work was performed. Entries in the log shall be in chronological order.

128. GMPs - History and the 2008 Revisions What does GMP mean to me? Revisions 211.188 Batch production and control records (b) (11) Identification of the persons performing and directly supervising or checking each significant step in the operation, or if a significant step in the operation is performed by automated equipment under § 211.68, the identification of the person checking the significant step performed by the automated equipment .

130. GMPs - History and the 2008 Revisions What does GMP mean to me? Why were GMPs initiated? Regulations don’t happen on their own Events precipitate them

131. GMPs - History and the 2008 Revisions What does GMP mean to me? Thank you Frank Settineri Veracorp LLC [email_address] 908-499-5540

132. GMPs - History and the 2008 Revisions What does GMP mean to me? References 1. www.fda.gov/opacom/backgrounders/miles.html 2. www.cfsan.fda.gov/~lrd/history1.html 3. Weschsler, J pp. 40-42 Pharmaceutical Executive January, 2007 http://pharmexec.findpharma.com/pharmexec/Legislation/Washington-Report- A-Full-Plate/ArticleStandard/Article/detail/395591 4. http://www.fda.gov/oc/history/makinghistory/firstgmps.html 5. http://www.foodsafety.gov/~lrd/histor1b.html 6. (Federal Register / Vol. 73, No. 174 / Monday, September 8, 2008 /Rules and Regulations pp. 51919-51933) http://www.fda.gov/OHRMS/DOCKETS/98fr/E8-20709.pdf 7. http://www.microbiologyforum.org/PMFNews/PMFNews.14.12.0812.pdf 8. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01657.html