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New
Manufacturing Principles for Medicinal Products
Introduction
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The Therapeutic Goods Administration (TGA)
currently licenses the manufacture of medicinal products in Australia in
accordance with the Australian code of Good Manufacturing Practice for
Medicinal Products (dated 16th August, 2002).
On the 29th July 2009, the Australian
government legislated the implementation of a new set of manufacturing
principles under the Therapeutic Goods (Manufacturing Principles)
Determination No. 1 of 2009. This determination (with some minor
exceptions) effectively replaces the current code with the Guide to Good
Manufacturing Practice for Medicinal Products (PE009-8) (dated 15th
January, 2009) published by the Pharmaceutical Inspection Co-operation
Scheme (PIC/S). |
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The updated principles are scheduled to become mandatory for all
manufacturers of medicinal products (who are subject to the TGA) on 1st
July 2010. In the interim, the TGA will accept compliance with either
the existing manufacturing principles, or the updated principles.
Table 1: Implementation dates for Therapeutic Goods (Manufacturing
Principles) Determination No. 1 of 2009 Date Active TGA code of GMP for
Medicinal Products Prior to 29th July 2009 Australian code of GMP (Aug
2002) 29th July 2009 to 30th June 2010 Australian code of GMP (Aug 2002)
or PIC/S Guide to GMP (Jan 2009) 1st July 2010 PIC/S Guide to GMP (Jan
2009) |
Why
is the TGA changing to the PIC/S GMP guide?
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The change to the PIC/S Guide has been an
ongoing process for the TGA over many years; the existing code is
actually a slightly modified version of the PIC/S Guide published in
January 2002. There are currently 35 national authorities participating
in the PIC/S scheme, as well as several international authorities,
including the World Health Organisation (WHO). From the TGA’s
perspective, participation in PIC/S is useful in several ways; most
importantly: |
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It preserves Australia’s equivalence with
international regulatory partners required under Mutual Recognition
Agreements (MRAs) for GMP certifications.This allows TGA certification
of Australian companies to be recognised internationally, and
certification by authorities with MRAs to be recognised in Australia. To
put it simply, different national authorities can audit on behalf of
each other. It
reduces the regulatory burden on Australian manufacturing companies
competing overseas, by minimising the requirement to comply with
different codes for different countries. |
The
mission of PIC/S is ’to lead the international
Who
is affected by the changes?
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The updated principles apply to all medicinal product manufacturers
previously subject to the Australian Code of GMP (2002). Active
Pharmaceutical Ingredient (API) manufacturers under TGA jurisdiction are
also affected, however they are not
addressed by this white paper.
The updated principles do not apply to manufacturers of the following
product types: Blood, blood components, plasma and haematopoietic
progenitor cells - For these products, there is no change to existing
compliance arrangements. The related Annex 14 of the new guide will not
come into force with the rest of the document. |
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►Veterinary products - Annexes 4 & 5 (veterinary products) have been
published in full in the new guide, but are not enforceable by the TGA.
The Australian Pesticides and Veterinary Medicines Authority (APVMA) is
still the regulatory authority for veterinary medicines in Australia.
►Human tissue - There is no change to existing compliance arrangements
for these products. The new guide makes no reference to human tissue
products.
►Therapeutic devices - There is no change to existing compliance
arrangements
for these products. The new guide makes no reference to therapeutic
devices. |
What
are the key changes in the new code?
There
are numerous changes in the updated code—some will have little impact on
manufacturers, while some changes are significant. The key changes are
summarised below:
Product quality review
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The new code includes product quality
reviews—companies with experience in FDA compliance will be familiar
with these. This is the first time that the TGA has required such
reviews. Product quality reviews should be performed annually for all
licensed medicinal products (including export only products). The new
code includes prescriptive details of the review requirements. |
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Reviews, as a minimum, must consider starting materials (including
packaging), inprocess and finished product results, batch failures,
significant deviations, changes to process and analytical methods,
marketing authorisation variations, stability results,
complaints and recalls, corrective actions, post-marketing commitments,
equipment qualification status and contractual arrangements (for
contract manufacturers). It is also expected that each review is
evaluated and assessments made on need (or otherwise) for corrective and
preventative action, including re-validation. Allowance is given for the
grouping of reviews by product type (e.g. solid dose, sterile,
etc.) where ‘scientifically justified’. It should be understood,
however, that each individual licensed product must be reviewed and
assessed fully, even when part of a grouped report. |
Ongoing stability program
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The previous code briefly mentions the expectation that stability
monitoring should
form part of a GMP compliant quality control program. The new code
expands
considerably on this concept and provides detailed instructions on what
is expected,
leaving little to interpretation.
The new code includes requirements for protocol content, number of
batches,
frequency of testing, reporting and investigation.
The expanded requirements for an ongoing stability program are
complimented by the
new Annex 19 (Reference & Retention Samples), which provides information
on the
reference and retention samples. |
Quality risk management
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Detailed information on quality risk management has been included as a
new, voluntary approach, to demonstrate compliance with the code.
The new Annex 20 (Quality Risk Management) provides more than 25 pages
of information detailing quality risk management concepts, methodology,
applications, definitions, references and examples. Note that, at this
stage, quality risk management is considered a voluntary part of a GMP
compliant quality management system. Its inclusion in the code indicates
that early adoption of this approach is likely to be beneficial in the
future. |
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References
►TGA Document: MP1/2009,
Title: Therapeutic
Goods (Manufacturing Principles) Determination No. 1 of 2009
►www.tga.gov.au/manuf/mpupdate.htm, Title:
TGA Information for Manufacturers: Updated manufacturing principles for
medicinal products
►Australian Code
of GMP for Medicinal Products (16 Aug 2002)
►PIC/S Document:
PE009-8 & Annexes
PIC/S Guide to
Good Manufacturing Practice for Medicinal
Products (15 Jan 2009)
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