Complaints , quality defects & recalls - New EMA Requirements

This presentation is compiled by “ Drug Regulations”
a non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
11/11/2014 1

 This presentation is compiled from freely
available resource like the website of EMA.
“Drug Regulations” is a non profit
organization which provides free online
 Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
11/11/2014 2
Drug Regulations : Online
Resource for Latest Information

◦ Extensive changes have been made to Chapter 8,
Part1, Vol 4. Now
◦ Quality Risk Management principles are required to
be used for
 Investigation of quality defects or complaints
 Decisions about product recalls
 Decision about risk-mitigating actions.
11/11/2014 3

 Significant emphasises on
◦ Investigation of the cause(s)
◦ Determination of the cause(s)
◦ Appropriate preventative actions to prevent
recurrence
◦ Expectations and responsibilities to report quality
defects to the Competent Authorities.
11/11/2014 4

◦ Article 47 of Directive 2001/83/EC on the Community
code relating to medicinal products for human use
◦ Article 51 of Directive 2001/82/EC on the Community code
relating to veterinary medicinal products.
◦ This document provides guidance for the interpretation of
the principles and guidelines of good manufacturing
practice (GMP) for medicinal products as laid down in
Directive 2003/94/EC for medicinal products for human
use and Directive 91/412/EEC for veterinary use.
11/11/2014 5

 Protect public and animal health
 Have a system and appropriate procedures to
◦ Record, assess, investigate and review complaints
including potential quality defects
◦ Effectively and promptly recall medicinal products
for human or veterinary use and investigational
medicinal products from the distribution network.
11/11/2014 6

 Apply Quality Risk Management principles to
 Investigation and assessment of quality defects
 Decision-making process for product recalls
 Corrective and preventative actions
 Other risk-reducing actions
11/11/2014 7

 Inform concerned competent authorities
◦ Confirmed quality defect which may result in product recall
or an abnormal restriction in the supply :
 Faulty manufacture
 Product deterioration
 Detection of falsification
 Non-compliance with the marketing authorisation or product
specification file
 Any other serious quality problems
11/11/2014 8

 Any other serious quality problems with a medicinal or
investigational medicinal product situations where
product on the market is found to be non-compliant
with the marketing authorisation,
11/11/2014 9

 Do not notify concerned competent
authorities if
◦ The degree of non-compliance satisfies the Annex
16 restrictions regarding the handling of unplanned
deviations.
11/11/2014 10

 Outsourced activities
 Contract should describe the role and
responsibilities of the
◦ Manufacturer
◦ Marketing authorisation holder
◦ Sponsor
◦ Any other relevant third parties
11/11/2014 11

 Describe in roles & responsibilities
◦ Assessment
◦ Decision-making
◦ Dissemination of information
◦ Implementation of risk-reducing actions
 Guidance contracts is provided in Chapter 7.
11/11/2014 12

◦ Address how to contact those responsible at each
party for the management of quality defect and
recall issues.
11/11/2014 13

 Personnel
◦ Appropriately trained
◦ Experienced
 Responsible for
◦ Managing complaint
◦ Quality defect investigations
◦ Measures to manage any potential risk(s) & recalls
 Independent of the sales and marketing organisation
11/11/2014 14

 Personnel
◦ Should include QP
◦ If not make QP aware of
 Investigations
 Risk-reducing actions
 Recall operations
11/11/2014 15

 Make available sufficient trained personnel &
resources for
◦ Handling
◦ Assessment,
◦ Investigation
◦ Review
◦ Implementing risk-reducing actions
◦ Management of interactions with competent authorities
11/11/2014 16

 Use
◦ Inter-disciplinary teams
◦ Quality Management personnel
11/11/2014 17

 Central Management of complaint and quality
defect
◦ Document roles and responsibilities of the
concerned parties
◦ Prevent delays in the investigation and management
of the issue.
11/11/2014 18

 Have written procedures
◦ Describe actions to be taken
◦ Document all complaints
◦ Assess if they represent a potential quality defect or
other issue.
11/11/2014 19

 Pay special attention
◦ Whether a complaint or suspected quality defect
relates to falsification.
11/11/2014 20

 All complaints do not represent actual quality
defects
 Such complaints should be
◦ Documented appropriately
◦ Communicated to responsible person
◦ Investigated
◦ Managed appropriately
 (e.g. suspected adverse events )
11/11/2014 21

 For such complaints
◦ Have procedures in place
◦ Investigate the quality of a batch
◦ Support an investigation into a reported suspected
adverse event
11/11/2014 22

 Procedure for Quality Defect Investigation should address
◦ The description of the reported quality defect.
◦ The determination of the extent of the quality defect.
◦ Consideration of checking or testing of reference and/or retention
samples
◦ A review of
 Batch production record
 Batch certification record and
 Batch distribution records (especially for temperature-sensitive
products)
11/11/2014 23

 Procedure for Quality Defect Investigation
should address
◦ Need to request a sample
◦ Need for the return of the defective product from
the complainant
◦ Need for an appropriate evaluation of the sample if
available
11/11/2014 24

 Procedure for Quality Defect Investigation should
address
◦ Assessment of the risk(s) posed by the quality defect
 Based on the severity and extent of the quality defect.
◦ Decision-making process to address risk reducing
actions in the distribution network
 Batch or product recalls
 Other actions.
11/11/2014 25

 Procedure for Quality Defect Investigation should
address
◦ Impact assessment of recall on availability of product
◦ Need to notify the relevant authorities of such impact
◦ Internal and external communications about quality
defect and its investigation.
11/11/2014 26

 Procedure for Quality Defect Investigation
should address
◦ Identification of the potential root cause(s)
◦ Corrective Action
◦ Preventative Actions
◦ Assessment of the effectiveness of CAPAs.
11/11/2014 27

 Investigations should be
◦ Recorded with all original details
◦ Documented with validity and extent of all reported
quality defects
◦ Assessed in accordance with Quality Risk Management
principles
◦ Investigated and action taken based on Risk
management principle
11/11/2014 28

 Investigations should be
◦ Extended to other batches
◦ Extended to other products in some cases
◦ Extended to other batches which may contain
portions of the defective batch or defective
components
11/11/2014 29

 Investigations should include review of
◦ Previous quality defect reports
◦ Any other relevant information
◦ Specific or recurring problems
◦ Further regulatory action if necessary
11/11/2014 30

 The decisions after investigations should
reflect the
◦ Level of risk that is presented by the quality defect
◦ Seriousness of any non-compliance with
 Marketing authorisation
 Product specification file
 GMP.
11/11/2014 31

 Decisions should
◦ Be timely
◦ Ensure that patient and animal safety is maintained,
◦ Be commensurate with the level of risk that is
presented by those issues
11/11/2014 32

 Comprehensive information not available at
early stages of an investigation
 Decision-making should ensure appropriate
risk-reducing actions
 Document all decisions taken as a result of a
quality defect
11/11/2014 33

 Report Quality defects in a timely manner to
◦ Marketing authorisation holder
◦ Sponsor
◦ All concerned Competent Authorities
 if recall anticipated
 In an abnormal restriction in the supply of the product
11/11/2014 34

 Apply root cause analysis work during
investigations.
 When true root cause(s) cannot be
determined, identify the most likely root
cause(s)
 Address root cause or most likely root cause
11/11/2014 35

 Formally justify human error if suspected or
identified as the cause
 Do not overlook
◦ Process
◦ Procedures
◦ System-based errors
11/11/2014 36

 CAPAs
◦ Appropriate Identification
◦ Correct implementation
◦ Monitor & assess for effectiveness
11/11/2014 37

 Review Quality defect records
 Perform trend analyses regularly
 Look for any indication of specific or
recurring problems requiring attention
11/11/2014 38

 Procedures
 Well written & established
 Regularly reviewed
 Updated when necessary
11/11/2014 39

 Regard any retrieval from the distribution
network as recall
 Manage this retrieval as recall.
 Retrieval or return of samples from
distribution for an investigation is not recall
11/11/2014 40

 Recall operations
◦ Capable of being initiated promptly at any time.
◦ Initiate without establishing root cause to protect
public or animal health
11/11/2014 41

 Batch/product distribution records
◦ Readily available
◦ Contain sufficient information on wholesalers and directly
supplied customers
 Addresses
 Phone and/or fax numbers inside
 Outside working hours,
 Batches
 Amounts delivered
 Exported products and medical samples
11/11/2014 42

 Investigational medicinal products
◦ Identify & inform all trial sites and the countries of
destination
◦ If a marketing authorisation has been issued inform the
marketing authorisation holder
◦ Implement a procedure for the rapid unblinding of blinded
products
◦ Disclose the identity of the blinded product only in so far as
is necessary.
11/11/2014 43

 Recall
◦ Consult concerned Competent Authorities,
◦ Determine how far a recall action should extend
◦ Take into account the potential risk to public or animal
health
◦ Inform Competent Authorities when there is no recall
due to batch expiration
 Such as with short shelf-life products
11/11/2014 44

 Inform Competent Authorities in advance
◦ For very serious issues a recall without prior
intimation is acceptable.
◦ Agree these in advance with concerned Competent
Authorities
11/11/2014 45

 Evaluate if recall may affect different markets in different ways
 Develop appropriate market-specific risk-reducing actions
 Discuss with concerned competent authorities
 Consider the risk of shortage of a medicinal product before recall
 Any decisions not to execute a risk-reducing action which would
otherwise be required should be agreed with the competent
authority in advance.
11/11/2014 46

 Recalled products
◦ Identify distinctly
◦ Store separately in a secure area
◦ Make & document formal disposition
◦ Discuss rationale for rework with competent authority
◦ Document the rationale for rework
◦ Evaluate the shelf life of reworked batches carefully
11/11/2014 47

 Record progress of recall process
 Issue closure and a final report
 Reconcile delivered and recovered quantities
 Periodically evaluate arrangements for recall
◦ Ensure they are robust & fit for use
 Evaluation should cover office & non office hours
 Evaluate the need for mock recall
 Document and justify mock recall
11/11/2014 48

 Other risk-reducing actions
 Issuance of cautionary communications
 Consider on a case by- case basis
 Discuss with concerned competent
authorities.
11/11/2014 49

 This presentation was compiled from freely
available resource like the website of EMA.
“Drug Regulations” is a non profit
organization which provides free online
 Visit http://www.drugregulations.org for
latest information from the world of
Pharmaceuticals.
11/11/2014 50

Complaints , quality defects & recalls - New EMA Requirements

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