EU GMP Part 1 : Chapter 5, Review of the latest update IPEC Europe Annual Seminar 5 February 2015 Nice
EU GMP Part 1 : Chapter 5,
Review of the latest update
IPEC Europe Annual Seminar
5 February 2015
Nice
EU GMP Part 1
• Basic Requirements for Medicinal Products
– Presented in 9 chapters
– Recently updated
– Chapter 3 Premises and Equipment
– Chapter 5 Production
– Chapter 8 Complaints and Product Recall
Revision Timetable
• 17 Jan 2013: draft published and public consultation began
• 18 July 2013: public consultation closed
• 8 November 2013: public comments published on the
Commission website
• 13 August 2014: final version published
• 1 March 2015: deadline for coming into operation
Chapter 5 Revisions
• The revisions mainly cover the aspects of:
– Control of cross contamination Sections 17 to 21
– Management of starting materials Sections 27 to 30, 35 & 36
Chapter 5 Revision- Prevention of
Cross Contamination in Production
• Enhances the Quality Risk Management approach to
controlling cross contamination
• Defines 13 technical and 10 organisational measures to
control and limit the risk to patient safety
• Introduces the need to consider toxicological risk as well as
pharmacological risk
• Overall is less prescriptive in terms of dedicated facilities and
equipment, but more structured supporting data needs to be
presented
Chapter 5 Revision- Prevention of
Cross Contamination in Production
• Prevention of cross contamination also covered by
• Revision to Chapter 3
• Draft Guideline on setting health based exposure limits for
use in risk identification in the manufacture of different
medicinal products in shared facilities*
– EMA/CHMP/ CVMP/ SWP/169430/2012 November 2014
• * comes into effect on 14 June 2015
Chapter 5 Revision- Management of
Starting Materials
• NEW REQUIREMENT
• The selection, qualification, approval and maintenance of
suppliers………, should be documented as part of the
pharmaceutical quality system.
• Staff involved in these activities should have a current
knowledge of the suppliers, the supply chain and the
associated risks involved.
Chapter 5 Revision- Management of
Starting Materials
• RETAINED
• Where possible, starting materials should be purchased
directly from the manufacturer
Chapter 5 Revision- Management of
Starting Materials
• NEW REQUIREMENT
• Excipients which pose a particular risk………, should be
given similar attention as active substances
Chapter 5 Revision- Management of
Starting Materials
• NEW REQUIREMENT
• Excipients which pose a particular risk………, should be
given similar attention as active substances
• Excipients and excipient suppliers should be controlled
appropriately based on the results of a formalised quality risk
assessment based on Commission guidelines
Chapter 5 Revision- Management of
Starting Materials
• NEW REQUIREMENT
• Appropriate aspects of the production, testing and control,
including handling, labelling, packaging and distribution
requirements , complaints, recalls and rejection procedures
should be documented in a formal quality agreement or
specification
Chapter 5 Revision- Management of
Starting Materials
• NEW REQUIREMENT (FOR ACTIVE SUBSTANCES)
• More emphasis on supply chain traceability, which needs to
ne formally assessed and verified
• Audits of manufacturers and distributors of active substances
should be carried out to verify use of relevant GMP/GDP
• Audits should be of appropriate duration and scope and
carried out by the MAH or by another entity acting under
contract
Chapter 5 Revision- Management of
Starting Materials
• AMENDED TERMINOLOGY
• Only starting materials which have been released by the
Quality Control department and which are within their retest
period should be used
• ‘shelf life’ replaced by retest period
Chapter 5 Revision- Management of
Starting Materials
• NEW APPROACH
• Manufacturers of finished products are responsible for
testing of starting materials, but can use some or all of the
test results from the manufacturer.
• However this must be justified and documented, plus the
following five requirements should be met:
Chapter 5 Revision- Management of
Starting Materials
i. Attention given to distribution controls so that test results
are applicable to material as delivered
Chapter 5 Revision- Management of
Starting Materials
i. Attention given to distribution controls so that test results
are applicable to material as delivered
ii. The pharma company should perform audits, either by itself
or via a third party to ensure appropriate GMP is in place
Chapter 5 Revision- Management of
Starting Materials
i. Attention given to distribution controls so that test results
are applicable to material as delivered
ii. The pharma company should perform audits, either by itself
or via a third party to ensure appropriate GMP is in place
iii. A Certificate of Analysis should be provided signed by a
suitably qualified/experienced person at the
manufacturer/supplier to confirm compliance with the
agreed specification
Chapter 5 Revision- Management of
Starting Materials
i. Attention given to distribution controls so that test results
are applicable to material as delivered
ii. The pharma company should perform audits, either by itself
or via a third party to ensure appropriate GMP is in place
iii. A Certificate of Analysis should be provided signed by a
suitably qualified/experienced person at the
manufacturer/supplier to confirm compliance with the
agreed specification
iv. The pharma company should have experience in dealing
with the manufacturer, should review the history of supply
and consider any significant changes
Chapter 5 Revision- Management of
Starting Materials
i. Attention given to distribution controls so that test results
are applicable to material as delivered
ii. The pharma company should perform audits, either by itself
or via a third party to ensure appropriate GMP is in place
iii. A Certificate of Analysis should be provided signed by a
suitably qualified/experienced person at the
manufacturer/supplier to confirm compliance with the
agreed specification
iv. The pharma company should have experience in dealing
with the manufacturer, should review the history of supply
and consider any significant changes
v. The pharma company should perform full analysis at
intervals determined based on risk and compare results
with those reported by the manufacturer
Finally
• NEW SECTION ON PRODUCT SHORTAGES DUE TO
MANUFACTURING CONSTRAINTS
• Puts a responsibility on the licence holder to report to the
regulatory authorities any production issues which could lead
to a drug shortage