Nucro Technics Inc'

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HARMONIZATION OF THE USP, EP AND JP MICROBIAL
TEST METHODS
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• ( 1996 ) PHARMACOPEIAL
• HARMONIZATION
• Pharmac. Forum
• Vol. 29 (1) (Jan Feb 2003)

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• Pharmacopeial Discussion
• Group (PDG)
• (1989)

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• Representatives
• I. European Directorate for
• the Quality of Medicines
• in the Council of Europe

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• II. The United States
• Pharmacopeia
• Convention, Inc.

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• III. Japanese Pharmacopeia
• in the Ministry of Health

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• In 2001,
• World Health Organization
• joins the group as observer.

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• The PDG works to harmonize
• 1. Excipient monographs
• 2. General chapters

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• The PDG also works to maintain an optimal level
  of science consistent with protection of the
  public health.

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• What is the definition of
• H A R M O N I Z A T I O N ?

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• A pharmacopeial general chapter or other
  pharmacopeial document is harmonized when a
  pharmaceutical substance or product tested by the
  documents harmonized procedure yields the same
  results and the same accept/reject decision is
  reached.

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• Interchangeability where each Pharmacopeia will
  identify as such a monograph or general chapter
  and there is consensus.

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• Harmonization by attribute is where some
  elements of monograph or general chapter may be
  harmonized, but others may not.

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• Harmonization is not achieved until the text
  becomes official in all three pharmacopeias.

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• There is a 7 step process involved for
• Harmonization.

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• Stage 1 Identification
• Stage 2 Investigation
• Stage 3 Proposal for expert
• committee review

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• Stage 4 Official Inquiry
• Stage 5 Consencus
• 5A. Provisional
• 5B. Draft sign-off

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• Stage 6 Adoption
• Stage 7 Implementation

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• Revision of the Harmonized Excipient Monograph
  and General Chapter
• can be initiated because of

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• ? Public Health Safety reasons
• ? Insufficient supply of pharmacopeial-
  quality product on the market
• ? Specified analytical reagents or equipment
  are not available

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• ? New methods of preparation of
• products or reagents are not covered
• by the current monograph
• ? Analytical procedures can be replaced by more
  appropriate accurate, or precise procedures

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• In a Global Market everybody will benefit
• 1) Reduced development effort
• 2) Simplification of regulatory filings
• 3) Reduced release testing

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• Draft harmonization tests are published in the
• Pharmacopeial Forum.

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• Final harmonization texts are published in the
  latest edition
• Supplement or
• Interim Revision Announcement.

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• Harmonization as it effects the Microbial Test
  Methods
• 1. Bacterial Endotoxin (JP 7)
• 2. Microbial Contamination (EP 3)
• 3. Microbial Attributes (EP 3)
• 4. Sterility Tests (EP 6)

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• Bacterial Endotoxin
• Stage 7 (JP)
• Implementation Stage
• USP 23 Supplement 2
• JP 14th

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• 1. Bacterial Endotoxin Harmonized items
• ? Apparatus
• ? Preparation of standard endotoxin soln
• ? Preparation of sample solution
• ? Determination of Maximum Valid Dose (MVD)

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• 1. Bacterial Endotoxin Harmonization Methods
• Agreement for the following methods
• ? Gel Clot technique
• ? Photometric technique
• 1. turbidometric
• 2. chromogenic

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• 2. Microbial Contamination (EP)
• Stage 3

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• 3. Microbial Attributes (EP)
• Stage 3

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• 4. Sterility Tests (EP)
• Stage 6

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• Sterility testing changes
• have been published in a
• Fourth Interim Revision Announcement
• August 1, 2003

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• Some changes
• Increase incubation
• to 14 days
• for all sterilities

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• Growth promotion to be performed to each lot of
• ready-prepared medium, and
• each batch of medium prepared either from
  dehydrated medium
• or from ingredients

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• Positive controls
• (not more than 10 cfu)
• per organism
• must grow within 5 days

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• Wholesale changes
• in the minimum quantity
• of sample to be used
• for each sterility medium

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• These changes apply to
• - liquids,
• - creams and ointments
• - solids, and
• - medical devices

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• Changes in the minimum
• number of articles to be tested
• in relation to the number of articles in the
  batch.

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• ? ? ? ? ? ? ?
• Q U E S T I O N S .
• ? ? ? ? ? ? ?

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