Handling Pharmaceutical Technical Complaints

Global Standard Operating Procedure
GSOP 331038
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Number / Version: 331038-02
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Title: Handling of Pharmaceutical Technical Complaints (PTC)
Supersedes Number / Date: 331038-01
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Workflow Number: 83007942
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Doc #: 331038, Ver: 3, Legacy #: 260809, Effective Date: 04Apr17
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of a utility model or design.
GSOP 331038
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Contents
1. Purpose and Scope........................................................................................................ 3
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2. Responsibilities .............................................................................................................. 3
3. Execution ....................................................................................................................... 4
3.1 Social Media .......................................................................................................... 4
3.2 Receipt of Complaint.............................................................................................. 4
3.3 Initiation of PTCs.................................................................................................... 6
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3.4 Preliminary Evaluation of Complaint ...................................................................... 6
3.5 Complaint Sample.................................................................................................. 9
3.6 Complaint Investigation.......................................................................................... 9
3.7 Complaint Close-Out............................................................................................ 11
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3.8 Follow-Up and Reporting ..................................................................................... 13
3.9 Collaboration with PVRM ..................................................................................... 14
3.10 Reconciliations..................................................................................................... 17
3.11 Business Continuity ............................................................................................. 18
3.12 Process Summary - PTC Management Process.................................................. 19
3.13 Process Summary - PTC Investigation Process .................................................. 20
3.14 Process Summary - Batch Review....................................................................... 21
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4. Abbreviations and Definitions....................................................................................... 22

4.1 Abbreviations ....................................................................................................... 22
4.2 Definitions ............................................................................................................ 23
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5. References................................................................................................................... 25
6. Attachments ................................................................................................................. 25
7. Change History ............................................................................................................ 26
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GSOP 331038
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1. Purpose and Scope
The purpose of this document is to define the process for pharmaceutical technical
complaints (PTCs) regarding all flu products (Fluvirin, Flucelvax and the Agrippal and Fluad
platform products) and pandemic products generated from Legacy Novartis sites. The SOP
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covers all sources of external feedback on the quality of products including from customers,
health care professionals, wholesalers, distributors, third party companies, and Health
Authorities.
This procedure also includes the requirements for adverse event batch review/QA
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Investigation for medical complaints for intermediates/bulk products and finished products.
This GSOP does not cover:

 Returned goods due to shipments errors (e.g. wrong distribution of product)
site to the warehouse and distributor DO

 Temperature excursions occurring during the transport from the manufacturing
 All defects identified by duty of care check at warehouse and distributor for a
batch that is not yet on the market
 Complaints received from partners or third parties for intermediates such as
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antigen concentrate, bulk, etc unless otherwise specified in associated Third
Party Quality/PV Agreements
The above are considered deviations and should be managed accordingly.
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Note: All bioCSL inquiries should be forwarded to GRPAPPKVQAREDLANE@csl.com
2. Responsibilities
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 Any Seqirus employee receiving a technical complaint must forward if possible

directly to the central email address ptc.reporting@seqirus.com

 Personnel should be trained in the process for reporting complaints. If this
is not possible, the employee should contact the local PTC management
or Customer service.
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 Global PTC Manager (or designee) is responsible for

 Global Oversight of the complaints
 Conducting reconciliations (PV, CPOs QA, VCOs, call centers and
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external distributors)
 Initial triaging and recording complaints
 Delivering on a quarterly basis PTC trends to Supply Chain QA.
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GSOP 331038
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 QA PTC contact at the product release site is responsible for assessing initial
classification and ensuring the necessary investigations are performed and
approved within the agreed timelines. This includes site QA and R&D QA as
appropriate.
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 PV (Medical Reviewer/BRP) is responsible for evaluation of AEs. Details are
given in the relevant PV Cross Functional SOP, #303268.
 Production units, third party manufacturers and distributors are responsible
for supporting the investigation and evaluation of possible causes of product
defects and for making any identified corrections.
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 QA is responsible to ensure that internal and external partners are trained on
PTC handling accordingly.
 PV SPOC is responsible to re-direct request for PV assessment to the relevant
function.
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 Each QA site is responsible to have included in their local procedure the
requirement to formally delegate a deputy, when applicable.
3. Execution
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3.1 Social Media
If an associate identifies any communication on social media that indicates a potential

safety, efficacy or quality defect with a legacy Novartis flu product, this should be treated as
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a complaint and reported to ptc.reporting@seqirus.com
3.2 Receipt of Complaint

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The centralized contact for product complaint reporting is: ptc.reporting@seqirus.com .

Complaints may be reported by any associate to the centralized email contact address and
as such the complaint may be initially received in different written formats, including an email
notification or email attachment e.g. PTC form (attachment 1) or as part of an Adverse Event
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form (example in Work Instruction 332124), or directly entered into the PTC computerized
system. If using the Sentry computerized system, refer to further instructions in 266716,
“Sentry Pharmaceutical Technical Complaint (PTC) System Use”.
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GSOP 331038
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The following intake information should be obtained:
 Date complaint reported / Complaint received by [name]
 Date of occurrence
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 Product Information:
 Product / Dosage form
 Batch Number
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 Impacted component
 Number of packages / number of units complained
 Sample available (yes/ no?)
 Availability of original packaging? (yes/no)
 Reporter Information


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Name / Company Information / Address incl. Tel-No / Fax-no and e-mail
Type of complainant (predefined selection values)
 Health Authority involved (yes / no?)
 Complaint description
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 Free text field
 Question: Is the complaint reported with an Adverse Vaccine Reaction?
(yes / no)
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 Question: Has the vaccine been administered? (yes/no)

 Was a partial or full dose administered?
 Administrative Information (Seqirus internal)
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 Date received by QA
 Unique PTC-Number
 Customer requested feedback? (yes/no)
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3.2.1 Requests from business partners of Seqirus supplied antigen concentrates and
intermediates will be investigated as requested per Quality/PV agreements.
Note: Investigations related to business partners will not be included in
Seqirus metrics.
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3.3 Initiation of PTCs
Each complaint recorded in the PTC computerized system will be assigned a unique number
by the Global PTC Manager within 1 business day of receipt. Refer to Section 3.12: Process
Summary for PTC Management Process for an overview and Section 3.13: for the Process
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Summary of the PTC Investigation Process.
An acknowledgement of receipt of a complaint including the assigned unique PTC number

should be sent to the complainant not later than 7 calendar days after receipt of the
complaint together with information that the complaint will be investigated, or a request to
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the reporter for further dissemination to the complainant. The acknowledgement letter
and/or email should be archived electronically in Sentry.
Technical complaints for clinical trials are communicated to the PTC management mailbox in
accordance with SOP 209953, “Managing Pharmaceutical Technical Complaints Reported
procedure. DO
During Clinical Trials”. All other aspects of the PTC are managed according to this
Technical complaints reported during clinical trials will be managed in collaboration with
R&D QA. R&D QA is the PTC owner and responsible for initiation of investigations.
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The collaboration will be based on investigations and actions involving the following entities:
 Clinical sites
 Clinical departments
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 Supplier of the trial products

Additionally, PTCs arising from clinical trials and related to concomitant medications,
competitor’s drugs and placebo in their original presentation will be recorded in Sentry for
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information only. In case the Non-Seqirus product is unpacked and re-packed for clinical trial
purposes, the investigation on the secondary packaging operations will be performed

(owned by R&D QA).
3.4 Preliminary Evaluation of Complaint

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QA performs preliminary evaluation to determine whether a reported PTC might be related

to a medical complaint, i.e. could be an adverse event or lack of efficacy/vaccine failure or
be associated with other PV relevant safety information as described in SOP 209821
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“Reporting Adverse Events and any other PV relevant Safety Information to the local NHP
Country Pharma Organization”. As soon as the medical impact has been identified and/or
confirmed, the request for PV reference should be sent within 1 business day. The following
points have to be considered during the medical impact assessment:
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GSOP 331038
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If the vaccine was administered to the patient/has possible medical impact the PTC must be
forwarded to the Pharmacovigilance & Risk Management (PVRM) department. PVRM will
provide their unique reference number within 2 working days. The Argus number should
also be provided by central case processing as soon as it is available. The central mailbox
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AE.reporting@seqirus.com should be used for this exchange.
If the vaccine was NOT administered to the patient and is classified as a “critical PTC”, QA
must notify PV (brmp@seqirus.com). PV will initiate actions as needed.
For PTCs, a thorough investigation must be initiated by gathering information as required
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from experts at the site of manufacture whether internal Seqirus or a third party. The
information must be documented and the outcome sent back to the complainant.
Responsible reporting entity (CPO QA/distribution partner) forwards technical or potentially

mixed complaint including any LOE or vaccination failure cases to the central email address
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ptc.reporting@seqirus.com. The responsible reporting entity will forward any AEs to PVRM.
If the PTC description is lacking detail, QA has to make efforts to obtain such details. The
following information is discussed and requested for the complaint report:
 Product name, strength, batch number
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 Complainant type, e.g. patient, hospital, pharmacy
 Complainant address and contact
 Description of complaint as reported
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 Nature of complaint with description(technical and/or medical)

 Complaint sample preferably in original packaging
 Pictures of complaint samples
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 Request for return of product involved preferably in the original packaging

 Any additional details available about the product relevant to the complaint
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The following must be identified subsequently as applicable:

 Possibility of (suspect) counterfeit, tampering or unauthorized sale, if applicable
 Categorization of the technical complaint regarding its criticality (i.e. critical, major
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and minor)
 Whether the complaint represents an event which is required to be reported to
the Health Authorities
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GSOP 331038
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 Necessity for further investigation
 Assurance that all information is promptly delivered to the relevant quality unit,
medical safety department, manufacturing site or reporting unit.
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Examination or testing of retained samples or returned products in support of a complaint
investigation must be defined in a local procedure.
An initial criticality classification (minor, major, critical) of the complaint must be done within
2 calendar days of receipt to assure appropriate communication and notification, as
required. Day of receipt of complaints by QA for evaluation is considered Day 0.
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Critical complaints should be notified in accordance with 289828, Management Escalation.
Additionally, in case of critical PTC related to clinical trials the following functions should also
be notified immediately after being evaluated as critical:
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 Senior Vice-President, Global Research and Development
 Vice-President, Clinical Development
 Vice-President, Quality
 Senior Director, Research and Development Quality
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Where the batch number is not known, the following steps should be attempted:
 All attempts should be made by QA for getting additional information regarding
the case.
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 Effort should be made to identify what batches were produced during the given
time frame(s) indicated and shipped to the concerned countries.
 In the case further information is received or if the number of batches was
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narrowed down an investigation as described in section 3.6 should be performed.

In the case the batch is not identified and all attempts to get additional information are not
successful, it should be evaluated if there is any aspect of the manufacturing process which
could potentially be correlated to the root cause of the reported PTC.
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All the actions performed need to be tracked and documented in the respective PTC file.
Regular monitoring and overall evaluation of PTCs received has to be performed and shared
with Quality management. These include trend reports e.g. on complaint categories and root
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cause & KPIs.
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GSOP 331038
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3.5 Complaint Sample
Due diligence (at least three documented attempts) must be made in attempting to retrieve
the complaint sample via the PTC intake entity or directly from the complainant; these
attempts must be documented in the Sentry complaint file.
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3.6 Complaint Investigation
QA PTC assigns the appropriate Seqirus departments using Sentry or email (for third
parties, as applicable), to perform the necessary investigations within the agreed timelines.
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While all complaints must be investigated, root cause analysis may not be needed. Each
complaint must be evaluated to determine if an investigation requires a root cause analysis.
Evaluation may consider information, such as:
 Trending
 Availability of adequate information
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 Continuing improvement activities to know product defects
 Confirmation of complaint
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In cases where an investigation is not required, a justification must be documented.
The investigation of critical complaints must be treated in an expedited manner, taking

priority over other investigations. In addition, for complaints with a known or potential safety
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impact, an initial investigation to determine market impact and related actions must be
performed within 3 calendar days of initiation of the investigation (within 5 calendar days
from receipt of complaint).
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If, during the investigation of a critical complaint, it is indicated that the complaint is a non-
critical complaint, it may be re-categorized, and the investigation then follows the process for
investigation of non-critical complaints.
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If at any time during the investigation of a non-critical complaint, it is indicated that the
complaint is a critical complaint, it is immediately elevated to critical status, and notification
escalated as per 289828. The investigation then follows the process for investigation of
critical complaints. If, during the investigation of a critical complaint, it is indicated that the
complaint is a non-critical complaint, it may be re-categorized with supporting justification,
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and the investigation then follows the process for investigation of non-critical complaints.
All complaint Lead investigators, investigation reviewers, and investigation approvers must
be certified to perform the respective functions. Details for the certification training are given
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in 298276, “Complaint and Deviation Investigation Training and Certification for Investigators
and Approvers” and in associated local procedures.
Each complaint whether technical or medical must be investigated in accordance with local
procedure to determine whether there is a confirmed product quality defect. In this case the
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root cause for the defect must be assessed, corrective actions defined and all must be fully
documented. The investigation must include consideration of review of manufacturing and
packaging batch records, equipment and facilities used, all relevant testing results,
examination of retain samples, and review of stability data.
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If a product defect is discovered or suspected in a batch, consideration must be given if
other batches or products need to be checked for the same aspect.
Trending is always checked and the presence of potential negative signals should be
verified, at least when three similar events on the same batch is received. In addition,
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trending can be also performed in the case there is a defect of one of the components (e.g.
syringe, needle) and this component is used for several products. In this case, trending on
the component (e.g. syringe/needle) batch should be performed.
During the investigation based on the nature of the complaint (e.g. critical complaints),
inspection of final product retention samples must be considered. For defects involving
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components such as the needle, visual inspection may not be possible without breaching
the integrity of retain samples. In the case of destructive testing, a smaller retention sample
set may be examined.
For other cases where only a limited amount of retain samples are investigated or in case
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inspection of retention samples is not considered, a justification has to be documented. For

retain and returned samples, the evidence of performed inspection must be provided and
documented (e.g. child investigation or via specific template).
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In addition, the component retention samples should be considered for visual inspection; this
may be performed by Seqirus or by the component supplier.
All effort should be given to ensure a proper analysis complaint sample e.g. perform specific
identity test for any foreign particulate matter in case of a complaint concerning particles.
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Corrective and preventive actions should be defined for all complaints for which there are a
confirmed product quality defect i.e. the root cause was identified in accordance with the
local CAPA procedure.
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In the case no CAPA is defined, the reason should be documented.
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Corrective actions and preventive actions with open effectiveness checks do not prevent
closure of the complaint report.
In the case the complaint is related to a product whose manufacturing involves more than
one site, all the involved sites should be notified of the complaint and if applicable involved
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in the investigation, via a child record. In the case the complaint involves 3rd party
manufacturing sites, the request of investigation will be done via email.
Additionally, if a corrective or preventive action affects other sites, the concerned site(s)
should be involved in the definition of the CAPA.
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In case of critical complaints reported from an EU country concerning a centralized and
MRP product, the concerned EU Qualified Persons (QPs) and EU Qualified Person for
Pharmacovigilance (EU QPPV) are notified as per 289828, Management Escalation. If the
investigation has revealed a quality defect and subsequent regulatory action or need for
CAPAs summary. DO
communication to regulators, the QPs are supplied with the investigation report and related
For US distributed products, if the root cause of a confirmed complaint is determined to be

due to a deviation or undetected event that occurred during production, testing, holding or
distribution and the defect potentially impacts safety, potency or purity of product, then a
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Biological Product Deviation Report must be filed in accordance with 292580.
At any stage of the investigation PVRM should be informed if a potential medical complaint
is suspected arising from the technical complaint investigation. In this case, the medical
complaints have to be sent to the PVRM central mailbox (AE.reporting@seqirus.com).
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In the event a potential recall is triggered during the investigation the local SOP for recalls
and 289828, Management Escalation should be followed.
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3.7 Complaint Close-Out
Each department involved in the investigation issues a summary of the investigation,

including results and corrective measures taken or proposed corrective actions. Timelines
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should be assigned for these actions. The respective department is accountable for the
timely completion of the defined corrective actions.
QA assesses the individual summaries, draws the final conclusion and assembles a final
report, which is to be approved by QA (or QP) with the appropriate access. As applicable,
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and primarily for serious or key medical events, PV will provide a medical statement or
evaluation.
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QA informs the external complainant on the conclusion of the investigation in writing by
submitting the customer response letter to Commercial Operations, the CPO involved, and
call center, as applicable. Upon closure of a mixed complaint, QA will prepare a summary
using the Sentry Single Complaint Report. Within 1 business day of closure the Complaint
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Report must be provided to Pharmacovigilance, at a minimum, via the Processing Mailbox,
AE.Reporting@Seqirus.com, as necessary.
For all complaints, critical and non-critical, (including third party manufactured products), the
investigation should be completed and the complaint closed within 45 calendar days from
receipt of the complaint. Critical complaints must be investigated and closed as
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expeditiously as possible.
If an investigation is not completed and the complaint not closed within the 45 day
timeframe, an extension for further 45 calendar days can be requested. In this case, an
interim report must be prepared. A request for extension of the investigation must be
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authorized by the site QA Head, and notification of the complaint must be performed in
accordance with 289828, Management Escalation. This notification must be documented in
Sentry either in written form or through use of a validated system.
If a complaint cannot be closed within the 45 calendar days of an extension due to e.g.
ongoing investigations, additional extension for additional 45 days has to be requested (see
above).
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All complaints that are not closed within 45 days from initiation of the investigation must be
considered “overdue”, even if an extension has been approved.
Interim reports should include the following:
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 Current status of the investigation, including actions taken in the past 45 calendar
days
 Justification / rationale for extending the investigation an additional 45 calendar
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days
 Ongoing and planned actions, including timelines and responsibilities for the
actions
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 Responsibility for follow up-monitoring and ongoing reporting and notification

 Estimated timeline to completion of investigation and closure of complaint. Interim
reports must be included in the complaint file
All applicable regulations regarding reporting to Health Authorities must be followed.
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It may be necessary to re-open a complaint if a sample is received late or additional

information is received from the complainant after closure. QA will assess the need to re-
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open the PTC for further investigation and/or to include the additional information in the
complaint file.
Documentation and complaint sample is retained per applicable records retention policy.
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3.8 Follow-Up and Reporting
3.8.1 Local QA is responsible for:
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 Reporting the following monthly:
 Number of total complaints divided by critical, major, minor / per sites /
per product / per defects
 Overdue critical complaints
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 Description and CAPA for critical complaints
 Key trends (per batches / per defects / per products
 QA sites will also deliver to Quality Dashboard trends on open
complaints, on time complaints closure and overdue complaints
 Providing input into the APR/PQR
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 Follow up of open corrective actions as well as providing timely updates to PTC

management at the site.
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3.8.2 Global QA PTC Manager provides the following trending to QLT/GQC:

 Periodic KPI reporting with number of complaint received, number of critical
complaints
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 Quarterly Q1 and Q3, semi-annual and annual trend report - minimally including a
review of complaints for the first half of the year and annual , trend analysis and
CAPA effectiveness
 Status of open corrective actions and effectiveness of implemented corrective
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actions
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3.9 Collaboration with PVRM
3.9.1 QA Investigations
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PV Medical Reviewer, BRP may request a QA investigation from the manufacturing site
based upon the receipt of an AE in accordance with the PV Cross Functional SOP 303268.
Each request and investigation should be documented into the PTC computerized system
(Sentry) using the “Batch Review” workflow or by the local QA group according to local
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procedures. Refer to Section 3.14: Process Summary of Batch Review Process.
PV Medical Reviewer/BRP should provide the following information to the Global PTC
Manager specifying the investigation required:
 Product name, batch number (when applicable)
 Investigation required (e.g. batch review)
 Description of the AE
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 Medical evaluation and indication of potential root cause to drive the investigation
required (e.g. type of infection, bacterial type that could cause it)
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 Any additional details relevant to the QA investigation
QA investigations (batch reviews) should be conducted within 10 business days (20
business days if more than one manufacturing site involved) by the appropriate QA group
and a summary document provided to PV.
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As a minimum, the following aspects should be considered and reviewed during the
investigation:
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 Events occurred during the manufacturing of the batch that could be correlated to
the reported AE
 Deviations related to the concerned batch that could be correlated to the reported
AE
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 Analytical test results for the concerned batch i.e. LIMS entries, that could be
correlated to the reported AE
Based on the nature of the AE further aspects may need to be considered such as validation
status, other products or batches affected stability information, etc.
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In case of specific requests for investigation that are not described in the PVRM Cross
Functional SOP 303268, these should be performed using the information available and any
additional investigational direction provided by PVRM.
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A summary of the investigation and conclusion should be documented using the Sentry
batch review report and provided by QA to PVRM central case processing within 24 hours
after completion.
For both mixed complaints (PTC/AE) or investigations requested as a result of an AE, any
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significant follow up information including additional analytical test results or analysis of data
must be submitted to PVRM within 24 hours of availability and also included in the report
summary.
All specific medical events, including potential root causes, as defined in the PV Cross
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functional SOP 303268 need to be immediately notified to ptc.reporting@seqirus.com by
PVRM central case processing for investigation.
If no batch number is known, all attempts should be made to determine if the reported event
could be linked to a specific batch. The following steps should be attempted:
DO
 all attempts should be made for getting additional information regarding the case
(to be performed by PV central case processing)
 effort should be given to identify what batches were shipped to the concerned
countries in an appropriate timeframe based on the vaccine administration dates
In the case the above specifications are not met, and depending on severity of the adverse
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events reported, it should be evaluated if there is any aspect of manufacturing process
which could be potentially correlated to the root cause of the reported adverse event (e.g.
media fill and environmental monitoring review to ensure no contamination in the case of
reported Staphylococcus infection).
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If seasonal product and the season when the event occurred is known, a summary section
from the Annual Product Review for the year in question (if available), together with the list
of packed batches manufactured that year is reviewed in the QA investigation (Batch
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Review flow).
Check with Supply Chain how many lots were on the concerned market/country. If only one
batch carry out investigation according to workflow.
All the actions performed need to be tracked and documented in the Sentry PTC
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computerized system or in the corresponding system.
For INN cases (i.e. those case where neither brand name, nor a valid identifiable batch
number was provided by the report(s)), no investigation will be performed.
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For all other cases with missing information please refer to the flow diagram 3.14.
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3.9.2 Monthly PTC / AE Review
The Global PTC Manager is responsible to conduct a monthly review with PV to exchange
information on medical complaints and PTCs by product. The monthly review is required to
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assess all complaints and adverse events for the purpose of assuring that all AEs and PTCs
have been correctly identified and received by QA and PV. In preparation the following is
required:
 The Global PTC Manager must provide the PTC line listing to
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Pharmacovigilance (PV) approximately by calendar day fifteen (15) of the current
month for the previous months received complaints.
 The PTC line listing must indicate the AE unique number (e.g. Argus) for
any complaint with an associated adverse event
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 Listings are to be emailed AE.Reporting@Seqirus.com
 PV data management provides the Initial AE and FU listings to
ptc.reporting@seqirus.com by calendar day fifteen (15) of the current month for
the previous months received AEs and FUs
 The review should be completed prior to the end of the current month for the prior
ED
month's received complaints and adverse events
 Minutes will be published and signed by PV and the Global PTC Manager.
Minutes will be maintained by the Global PTC Manager.
The following items are included in the review:
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 Review of AE line listings

 Review of PTCs
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 Identification of any potential mixed complaints not previously identified during

the period
 Elements and metrics of the PTC/PV interface (e.g. response times,
improvements), as needed
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 Critical deviations that require monitoring of specific product batches in the

market (e.g. related to media failure and/or BPDR)
 Status of outstanding QA Investigations
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3.9.3 Training
Training on handling PTCs with potential medical impact should be provided by
Pharmacovigilance for all new personnel responsible for handling technical complaints
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(“PTC Contact Person”). Site/R&D PTC Management requests from Pharmacovigilance
training on identification of PTCs with potential medical complaints and has to ensure that all
new staff members are trained initially and on a yearly basis thereafter. This training
requirement must be assigned in the corresponding training plan/matrix of each staff
member. Once per year, a refresher training organized by the Global PTC Manager will be
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provided by PVRM to relevant QA staff.
3.10 Reconciliations
3.10.1 CPOs Reconciliation

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The Global PTC Manager will provide a monthly listing to all CPOs QA that are the license
holder or distributor of vaccine for review. The reconciliation will assure that all PTCs have
been received and there is no potential mixed complaints and/or technical complaints not
previously identified during the period.
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Outcome and action items from the review will be documented and archived by the Global
PTC Manager.
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3.10.2 VCOs Reconciliation

On a monthly basis, the Global PTC Manager is responsible for sending to the VCOs a
global listing of all PTCs. The reconciliation will assure that all PTCs have been received
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and there are no technical complaints that have been missed. Outcome and action items
from the review will be documented and archived by the Global PTC Manager.
3.10.3 External Distributors Reconciliation

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On a monthly basis, the Global PTC Manager is responsible for sending to the external
distributors a global listing of the PTCs for the countries they are responsible for. The
reconciliation will assure that all PTCs have been received and there are no technical
complaints that have been missed. Outcome and action items from the review will be
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documented and archived by the Global PTC Manager.
Page 17 of 32
GSOP 331038
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3.10.4 Call Center Reconciliation
On a monthly basis, the Global PTC Manager is responsible for sending to the Call Centers
(e.g. US, UK, and Germany) a global listing of all PTCs. The reconciliation will assure that all
PTCs have been received and there are no technical complaints that have been missed.
ME
Outcome and action items from the review will be documented and archived by the Global
PTC Manager.
3.10.5 Clinical Trials Reconciliation
CU
On a quarterly basis, a cumulative report of all PTCs arising from active clinical trials will be
provided to the respective Clinical Trial Teams for review and reconciliation to ensure that all
PTCs have been reported and received. Outcome and action items from the review will be
documented and archived by the Global PTC Manager.
3.11 Business Continuity DO

If Sentry is unavailable, the PTC Record Contingency Form (Attachment 2) or QA
Investigation Form (Attachment 3) must be used and a file maintained for each complaint
including any correspondence, additional analytical reports or data generated as a result of
ED
further testing of a returned sample or retention samples, and any other documentation
regarding the investigation, a unique number assigned and uploaded into Sentry when
available.
Date, product, batch # and description will be the unique identifier for tracking purposes until
LL
Sentry is available.
When Sentry is available, the PTC should be entered into Sentry for reporting and
investigation purposes. The PTC Record Contingency Form (Attachment 2) and QA
RO
Investigation Form (Attachment 3) should be attached to the record in Sentry.

NT
CO
Page 18 of 32
GSOP 331038
NT
3.12 Process Summary - PTC Management Process
ME
CU
DO
ED
LL
RO
NT
CO
Page 19 of 32
GSOP 331038
NT
3.13 Process Summary - PTC Investigation Process
ME
CU
DO
ED
LL
RO
NT
CO
Page 20 of 32
GSOP 331038
NT
3.14 Process Summary - Batch Review
PV requests QA
Investigation
ME
Batch and product Vaccination date and
No No
available country available
CU
No investigation will
be performed
Yes
DO
QA reviews lots
available in the
country
Yes
ED
QA uses general parameters
and data available (e.g.
Batch identified? No stability, trends, APR) to
make evaluation
LL
Yes
RO
QA performs
Investigation
NT
CO
Page 21 of 32
GSOP 331038
NT
4. Abbreviations and Definitions
4.1 Abbreviations

ME
AE Adverse Event
 APR Annual Product Review
 BPDR Biological Product Deviation Report
 CPO Country Pharma Organization
CU
 EU QPPV European Union Qualified Person for Pharmacovigilance
 GQC Global Quality Council
 FU Follow Up



INN
LOE
PMSO
Lack of Efficacy DO
International Non-proprietary Name
Post-Marketing Safety Operations (PMSO)

 PQR Product Quality Review
 PTC Pharmaceutical Technical Complaint
ED
 PVRM Pharmacovigilance & Risk Management
 QA Quality Assurance
 QP Qualified Person
LL
 SPOC Single Point of Contact

 VCO Vaccine Country Organization
RO
NT
CO
Page 22 of 32
GSOP 331038
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4.2 Definitions
 Adverse Event: Any untoward medical occurrence in a patient or clinical trial

subject administered a human medicinal product and which does not necessarily
have to have a causal relationship with this treatment. An adverse event can
ME
therefore be any unfavorable and unintended sign (e.g. an abnormal laboratory
finding), symptom or disease temporally associated with the use of a medicinal
product, whether or not considered related to the medicinal product.
 Adverse Drug Reaction: A response to a medicinal product which is noxious
CU
and unintended and which occurs at doses normally used in man for the
prophylaxis, diagnosis or therapy of disease or for the restoration, correction or
modification of physiological function.
 Complaint: Any verbal, written or electronic expression of dissatisfaction with the
DO
product identity, quality, stability, reliability, safety, efficacy, performance or
usage. A patient, pharmacist, health professional, etc. could make the report.
 Country Pharma Organization (CPO): The in-country responsible organization

for product distribution, customer interface, adverse event and PTC monitoring.
ED
 Medical Complaint: A report of an adverse event or lack of efficacy (vaccination
failure), or any PV relevant safety information as described in the PV Cross
Functional SOP 303268, that is observed with the use of the product.
 Mixed Complaint (PTC/AE): A reported event that includes both an adverse

LL
event/medical complaint and a Pharmaceutical Technical Complaint e.g. (a

reported case of blunt needle causing injection site pain). Reports of lack of
efficacy (vaccination failure) will be handled as mixed complaint as soon as a QA
RO
investigation request for the report has been received from the
Pharmacovigilance medical case reviewer or delegate.
 Pharmaceutical Technical Complaint: A report of a visual, organoleptic,

qualitative, quantitative or functional defect.
NT
 Product: All marketed Seqirus products, clinical samples, and parallel imported
products.
Note: Returned goods due to shipment errors or goods damaged during

CO
transport are not covered by this SOP.
Page 23 of 32
GSOP 331038
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 Critical Defect: A defect which has the capability to significantly affect the health
of the patient or has the potential to lead to a recall, such as:
 product mix-up
ME
 mislabelling
 missing label
 missing variable data on the label/ vignette or outer package
 tampering
CU
 contamination in medicinal product
 cross contamination
 leakages/cracked containers intended as a potential integrity closure fault
 suspected counterfeit
DO
 Major Defect: A defect which has moderate potential to affect the health of the
patient and lead to a recall. Major defects include complaints that affect the
integrity of the primary or secondary packaging or product or the product cannot
be appropriately used, such as:
 missing package insert
ED
 blunt needle
 bent needle
 plunger rod missing/not fixed properly
LL
 broken syringe, ampoule

 empty blister
 Minor Defect: A defect which has no capability to affect the health of the patient
RO
and is not likely to lead to a recall. Minor defects include complaints that are
cosmetic or aesthetic in nature which do not affect the integrity of the packaging
or product and the product can be appropriately used, such as:
 secondary packaging scuffed
NT
 secondary packaging soiled

 small defects to packaging such as inadequate perforation of the blister
 blister hard to open
 label hard to remove
CO
 bent protective cap but not bent needle
Page 24 of 32
GSOP 331038
NT
5. References
 339969, Seqirus Quality Manual
ME
 339979, Product Surveillance and Controls Quality Policy
 258018, Deviation and CAPA Management
 289828, Management Escalation
CU
 266716, Sentry Pharmaceutical Technical Complaint (PTC) System Use
 254318, Product Recall
 298276, Complaint and Deviation Investigation Training and Certification for
Investigators and Approvers


DO
292580, Reporting of NVD Biological Product Deviations
209953, Managing Pharmaceutical Technical Complaints Reported During
Clinical Trials
 209821, Reporting Adverse Events and any other PV relevant Safety
ED
Information to the local NHP Country Pharma Organization
 303268, Processes and Responsibilities Relating to QA Investigations
 WI 332124, Handling and Reporting Adverse Events by the US Medical
Communications Group
LL
6. Attachments
RO
 Attachment 1, PTC Complaint Form (sample)

 Attachment 2, PTC Record Contingency Form

 Attachment 3, QA Investigation Contingency Form
NT
CO
Page 25 of 32
GSOP 331038
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7. Change History
Section Changes Made Change Justification
Throughout  Converted to GSOP template  Updated MSOP to GSOP
document  Updated Novartis and NVx to  Company Name Change
ME
Seqirus as appropriate
 Updated central email address  CC 1014987
for PTC Reporting  To differentiate
 Updated QA PTC Manager to responsibilities
Global PTC Manager or Site
PTC Manager  Seqirus Quality Policies
CU
 Removed references to are governing documents
Novartis Quality Manuals and
Quality Directives
3.3, 3.11  Creation of initiation section  Separation of sections
and contingency section
3.7
3.8
DO
 Clarified requirements for
Mixed Complaint closure.
 Call Center Reconciliation
moved from section 3.8 to 3.10
 Clarity
 Group all reconciliation

requirements
3.9.1  Removed Standard and  CC 1016444 – Standard
Expanded Investigation term events do not require a QA
ED
Investigation
 Removed INN reconciliation  INN reconciliation will be
requirement confirmed by PV
3.11,  Created Business Continuity  Contingency if Sentry is
Attachments 2 Section unavailable
LL
and 3
3.12, 3.13. and  Streamlined flow chart  Transition to Seqirus
3.14
4.1  Removed abbreviations that  Abbreviations not captured
RO
are no longer relevant within procedure

Throughout  Updated PV contacts and  Administrative changes to

Document references align with new
Pharmacovigilance
structure
NT
Regulatory  Added Regulatory commitment  Administrative changes to

Commitment information into Regulatory include regulatory
Commitments table. commitment within table
Regulatory Commitments
CO
Version DR / CC / CAPA # Change History

1 1005268 Section 3.2; Receipt of Complaint; Inspection commitment to
clarify various sources of documentation are permitted for
PTC intake
Page 26 of 32
GSOP 331038
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Attachment 1: PTC Complaint Form
Report of Pharmaceutical Technical Complaint

To be sent to: ptc.reporting@seqirus.com
ME
Date Complaint Reported: Complaint Received By Name:
Date Complaint Occurred:
1. Product Information
Vaccine Product Name: Pharmaceutical Technical Complaint (PTC):
CU
Yes No Unknown
Batch Number: Complaint Sample Available? Yes No
Expiration Date: Photograph of Sample Available? Yes No
Impacted Component: Original package available? Yes No
Dosage Form: Number of Units Implicated:
2. Complainant Information
Name:
DO Number of Packages Implicated:
Pharmacy/Company Name: Type of Complainant:

Physician
Pharmacist
Address: Tel. No.: Nurse
Wholesaler
ED
Zip-Code: Fax No.: Hospital
Patient
Country: E-Mail:
Heath Authority - Reference #
Other:
3. Description of Complaint
LL
Is the complaint reported with an Adverse Vaccine Reaction/Adverse Event? Yes No

(If the complaint was reported with an Adverse Vaccine Reaction, please follow the procedure concerning the reporting of adverse
vaccine reactions and fill in the “Report on Suspected Adverse Vaccine Reaction” form as well)
Complaint Description as Originally Reported:
RO
Remarks/Additional Notes:
4. Product Administration
Was the product administered? Yes If so, Full Dose Partial Dose No Unknown
NT
5. Sample Tracking Information

Returned Sample Box Issued to Complainant Returned Sample to be sent to Seqirus:
Date: N/A Liverpool Holly Springs N/A
Number of Packages to be returned: N/A Customer Requested Feedback? Yes No
CO
Remarks:
6. Administrative Information
Sentry Record # N/A
Page 27 of 32
Page 1 of 3

GSOP 331038
NT
Attachment 2: PTC Record Contingency Form
Report of Pharmaceutical Technical Complaint
ME
Global PTC Manager will complete Section 1, Receipt of Complaint. The remainder of this form will be
completed by the manufacturing site PTC Contact and QA Approver. If initiation occurs at a site separate from
the responsible manufacturing site, the original form must be archived per local SOPs.
1. Receipt of Complaint/ Manual Tracking #
CU
A. General Information
Initiator Name Date Initiated
Complaint Received By Complaint Received
Person By Location
Received by Seqirus On Received by QA On
Complaint Received at
Site
Owner
Complaint Approver
DO Complaint
Responsible Site
Complaint Evaluator
Critical Complaint
Evaluator
Due Date Original Due Date
ED
B. Complainant Information
Complainant Name Complainant
Company
Complainant Address
Zip Code Complainant Country
Complainant Telephone Fax Number
LL
Number
Email Address Type of Complainant
C. Complaint Details
Complaint Description
RO
Product Name Campaign

Formulation Product Company
NT
Owner
Number of Packages Number of Units
Complained Complained
Complaint Sample Batch Information
Available
CO
Complained Batch Clinical Trial Number

Number
Initiator Signature/Date
Page 28 of 32
Page 2 of 3

GSOP 331038
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2. Complaint Evaluation
Medical Impact Adverse Event
Number
Dose Administered Forwarded to PVRM
ME
rd
Request Sent On 3 Party Involved Yes No
rd Investigation
3 Party Supplier
Requested On
Final Investigation Overall Risk
Received On Classification
PTC Yes No
CU
Investigation Plan
Immediate
Actions/Corrections
Related Records Health Authority Yes No
Involved
Health Authority Name Reference Number
Recall Required
BPDR/HA Notification
Evaluation Justification
DO BPDR/HA Notification
Required
Yes No
BPDR/HA Notification Recall Committee

ED
Reference Convened
Evaluator Signature/Date
3. Sample Analysis
Sample Requested Sample Received
Date(s) Sample Date Sample
LL
Requested Received
Sample Information
4. Trend Analysis
A. Trend Information
RO
Product Name Trend Identified

Trend Analysis
Trend Identified Category Level 1
Category Level 2 Category Level 3
5. Extension
Interim Report
NT
Date Extension Extension Count

Requested
Extension Justification
CO
Due Date QA Approval

Signature/Date
Page 29 of 32
Page 3 of 3

GSOP 331038
NT
6. Complaint Closure
A. Complaint Summary
Investigation Summary
Root Cause Summary
Complaint Root Cause Complaint Root
ME
Level 1 Cause Level 2
CAPA Summary
Conclusion
7. Customer Response Letter

Date On Letter
CU
Letter Customized Text
Owner Signature / Date
QA Approver
Signature/Date
Transfer to Sentry System
Sentry Event Number
Entered By
Signature/Date
Verified By
DO
Signature Date
ED
LL
RO
NT
CO
Page 30 of 32
Page 1 of 2

GSOP 331038
NT
Attachment 3: QA Investigation Contingency Form
Report of Batch Review related to an Adverse Event
ME
Global QA PTC will complete Section 1, Initiation. The remainder of this form will be completed by the
manufacturing site Owner/Investigator and QA Approver. If initiation occurs at a site separate from the
responsible manufacturing site, the original form must be archived per local SOPs.
1. Initiation / Manual Tracking #
Initiator Name Date Initiated
CU
Title Received On Date
Owner Serious Unexpected Yes No
BR Approver BR Responsible Site
Due Date
Event Description
DO Adverse Event Number
Product Name Campaign

ED
Formulation Complaint Country
Product Company Owner Batch Info

LL
Initiator Signature/Date
2. Batch Review
rd
3 Party Involved Yes No 3rd Party Supplier
RO
Review of Deviations To be performed when Sentry is available.
Review of BPR
NT
Review of LIMS Entries

CO
Review of Changes To be performed when Sentry is available.
Page 31 of 32
Page 2 of 2

GSOP 331038
NT
Review of Shelf-Life /
Stability
ME
Validation Status
Trend Analysis
CU
Related Records To be performed when Sentry is available.
Conclusion
Comments
DO
3. Batch Genealogy
ED
Batch Genealogy
Owner Signature/Date
LL
4. Batch Review Approval
Approver Signature/Date
5. Transfer to Sentry System

RO
Sentry Record Number
Entered By
Signature/Date
NT
Verified By
Signature/Date
CO
Page 32 of 32
Novartis
Controlled Document Approval Certificate /
Freigabenachweis kontrolliertes Dokument /
Certificazione per l’approvazione di un documento controllato
NT
The individuals listed have approved this document for implementation using an electronic signature in the
Atlas EDMS. / Die aufgeführten Personen haben durch ihre elektronische Unterschrift, dieses Dokument
im Atlas EDMS genehmigt. / Le persone sotto riportate hanno approvato questo documento per
consentirne l’utilizzo (l’approvazione avviene mediante firma elettronica su sistema Atlas EDMS).
ME
UserName: Atkins, Jessica (atkinje2)
Title: Global PTC Manager
CU
Date: Friday, 31 March 2017, 18:19 GMT
Meaning: Approved by Document Owner; responsible and accountable for the content of the document./ Genehmigung zum Einzug
durch Dokumenteninhaber; zuständig und verantwortlich für den Dokumenteninhalt. / Approvato dal Responsabile del Reparto;
assicura che le informazioni siano tecnicamente corrette.
================================================
UserName: McGhee, Iain (mcgheia1)
Title: Head of Quality Operations, Novartis Influenza
Date: Monday, 03 April 2017, 07:15 GMT
DO
Meaning: Approved by QA; responsible for compliance with internal and external requirements. /Genehmigung durch
Qualitätssicherung; verantwortlich für die Übereinstimmung mit internen/externen Qualitätsanforderungen./ Approvato da QA;
assicura che il contenuto del documento sia coerente con la filosofia di qualità Novartis.
ED
================================================
LL
RO
NT
CO
This signatur e certificate is only valid when accompanied by all the pages of the document. /
Dieser Nachweis ist nur zusammen mit allen Seiten des Dokumentes gültig. /
La presente certificazione è valida solamente se accompagnata da tutte le pagine del documento cui si riferisce

Handling Pharmaceutical Technical Complaints

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Handling Pharmaceutical Technical Complaints

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Global Standard Operating Procedure

Supersedes Number / Date: 331038-01

1. Purpose and Scope........................................................................................................ 3

4. Abbreviations and Definitions....................................................................................... 22

This GSOP does not cover:

site to the warehouse and distributor DO

Note: All bioCSL inquiries should be forwarded to GRPAPPKVQAREDLANE@csl.com

 Any Seqirus employee receiving a technical complaint must forward if possible

directly to the central email address ptc.reporting@seqirus.com

 Global PTC Manager (or designee) is responsible for

3.1 Social Media

If an associate identifies any communication on social media that indicates a potential

a complaint and reported to ptc.reporting@seqirus.com

3.2 Receipt of Complaint

The centralized contact for product complaint reporting is: ptc.reporting@seqirus.com .

 Question: Has the vaccine been administered? (yes/no)

An acknowledgement of receipt of a complaint including the assigned unique PTC number

 Supplier of the trial products

purposes, the investigation on the secondary packaging operations will be performed

3.4 Preliminary Evaluation of Complaint

QA performs preliminary evaluation to determine whether a reported PTC might be related

For PTCs, a thorough investigation must be initiated by gathering information as required

Responsible reporting entity (CPO QA/distribution partner) forwards technical or potentially

 Nature of complaint with description(technical and/or medical)

 Request for return of product involved preferably in the original packaging

The following must be identified subsequently as applicable:

narrowed down an investigation as described in section 3.6 should be performed.

cause & KPIs.

In cases where an investigation is not required, a justification must be documented.

The investigation of critical complaints must be treated in an expedited manner, taking

inspection of retention samples is not considered, a justification has to be documented. For

In the case no CAPA is defined, the reason should be documented.

For US distributed products, if the root cause of a confirmed complaint is determined to be

3.7 Complaint Close-Out

Each department involved in the investigation issues a summary of the investigation,

 Responsibility for follow up-monitoring and ongoing reporting and notification

It may be necessary to re-open a complaint if a sample is received late or additional

3.8.1 Local QA is responsible for:

 Follow up of open corrective actions as well as providing timely updates to PTC

3.8.2 Global QA PTC Manager provides the following trending to QLT/GQC:

computerized system or in the corresponding system.

 Review of AE line listings

 Identification of any potential mixed complaints not previously identified during

 Critical deviations that require monitoring of specific product batches in the

3.10.1 CPOs Reconciliation

3.10.2 VCOs Reconciliation

3.10.3 External Distributors Reconciliation

documented and archived by the Global PTC Manager.

3.10.5 Clinical Trials Reconciliation

3.11 Business Continuity DO

Investigation Form (Attachment 3) should be attached to the record in Sentry.

Post-Marketing Safety Operations (PMSO)

 SPOC Single Point of Contact

 Adverse Event: Any untoward medical occurrence in a patient or clinical trial

 Adverse Drug Reaction: A response to a medicinal product which is noxious

 Complaint: Any verbal, written or electronic expression of dissatisfaction with the

 Country Pharma Organization (CPO): The in-country responsible organization

 Mixed Complaint (PTC/AE): A reported event that includes both an adverse

event/medical complaint and a Pharmaceutical Technical Complaint e.g. (a

Pharmacovigilance medical case reviewer or delegate.

 Pharmaceutical Technical Complaint: A report of a visual, organoleptic,

Note: Returned goods due to shipment errors or goods damaged during

transport are not covered by this SOP.