eu gmp part 1 : chapter 5, review of the latest updateipec-europe.org/uploads/5_c_mroz.pdf · eu...

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.


Starting Materials

• RETAINED

• Where possible, starting materials should be purchased

directly from the manufacturer


Starting Materials

• NEW REQUIREMENT

• Excipients which pose a particular risk………, should be

given similar attention as active substances


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


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


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


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


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:


Starting Materials

i. Attention given to distribution controls so that test results

are applicable to material as delivered


Starting Materials



ii. The pharma company should perform audits, either by itself

or via a third party to ensure appropriate GMP is in place


Starting Materials





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


Starting Materials









iv. The pharma company should have experience in dealing

with the manufacturer, should review the history of supply

and consider any significant changes


Starting Materials









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

Thank you for your attention

eu gmp part 1 : chapter 5, review of the latest updateipec-europe.org/uploads/5_c_mroz.pdf · eu...

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