Responses to the results of pharmacovigilance system audits must be clear and concise and include proposed measures to address both the identified deficiency and the root cause of the non-compliance/deficiency.
Specific/clear
- the applicant must conduct a further assessment to determine the full extent of the non-compliance/deficiency.
- the applicant must consider not only how to correct the identified nonconformity/deficiency, but also the root cause of the problem.
Measurable
- the applicant must clearly define which corrective and preventive actions it plans in order to eliminate the identified non-conformity.
- specific results of the proposed corrective and preventive actions must also be stated, for example, an update of a standard operating procedure, a record of training conducted, etc.
Achievable/realistic
- the applicant must not make promises that it will not be able to keep, since the auditor will re-verify the implementation of corrective and preventive actions.
- the applicant must comply with the legislation, therefore this must be taken into account when developing the corrective and preventive action plan.
Time-bound
- the applicant must clearly state the schedule of corrective/preventive actions for each non-conformity/deficiency.
The applicant should also consider identifying and preventing other potential similar non-compliances/deficiencies in the pharmacovigilance system.
The applicant must provide responses to the results of the audit of pharmacovigilance systems directly in the table(s) of section 4.3.1., without changing the auditors' text describing the audit results. An example of text is given below as guidance when considering the information to be entered in each field of the table(s). "Not applicable" should be entered in the relevant field if the requested information does not correspond to the given result.
| Root cause analysis
The root cause(s) should be determined, after proper consideration of which recurrence of the non-conformity/deficiency can be prevented. There may be more than one root cause for any non-conformity/deficiency. |
| Further evaluation
An assessment should be provided of the extent to which the non-compliance/deficiency exists in the pharmacovigilance system and what impact this non-compliance/deficiency may have on all of the applicant's medicinal products. If necessary, it should be described what further assessment has been performed or may be required to fully assess the impact of the non-compliance/deficiency; for example, a retrospective data analysis may be required to fully assess the impact. |
| Corrective measure(s)
The actions that were taken/proposed to correct the identified non-conformity/deficiency must be described in detail. |
| Precautionary measure(s)
The actions taken/proposed to eliminate the root cause of the non-conformity/deficiency should be described in detail in order to prevent recurrence. Action(s) to detect and prevent other similar non-conformities/deficiencies should also be considered. |
| Work result(s)
The specific results of the proposed/implemented corrective and preventive actions should be described in detail. For example, an update of a standard operating procedure/work instruction, a record of retraining, an IT solution, etc. |
| Deadline(s)
The actual/proposed date(s) for the completion of each action should be indicated. It should be indicated when the action has been completed. |
Example of correct completion by the applicant of the table based on the results of the pharmacovigilance system audit
| Result SN |
“Process name” |
| 1) The job descriptions of the QPPV/deputy QPPV (hereinafter – JD of the QPPV/deputy QPPV) do not document the responsibilities regarding "AAA" for performing the delegated obligations and pharmacovigilance activities in Ukraine, as stated in the "Contractual document" (Agreement).
2) The current procedural document SOP “Procedure for updating information on medicinal products on the company website” needs further work, as it does not contain information on:
- identification of information sources;
- criteria determining the need to post/update information on the website;
- procedure for checking the relevance of information on the website.
Regulatory references:
• Procedure for Conducting Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 29 January 2007 under No. 73/13340 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996)
• Standard “Guideline. Medicinal products. Good pharmacovigilance practice. ST-N MOZU 42-8.7:2015”, approved by order of the Ministry of Health of Ukraine of 25 March 2015 No. 267 as amended by changes approved by order of the Ministry of Health of Ukraine of 05 April 2018 No. 620 |
| Root cause analysis |
| 1) The SOPs were drawn up for the enterprise by the HR department without the involvement of the QPPV/staff of the Pharmacovigilance Department, and the requirements of the current legislation in the field of pharmacovigilance and of the "Contractual Document" (Agreement) were not taken into account.
2) The SOP “Procedure for updating information on medicinal products on the company's website,” current version 01, was drawn up at the start of the organization of work – in 2018. The company provides for a scheduled review of the SOP every 5 years; the next review of the SOP “Procedure for updating information on medicinal products on the company's website” was scheduled for 2023. Also, the current quality system does not provide for an unscheduled review of the SOP. Therefore, the SOP “Procedure for updating information on medicinal products on the company's website” was not updated and did not contain all the information. |
| Further evaluation |
| 1) The job descriptions of the QPPV/deputy QPPV were reviewed for compliance with the "Contractual Document" (Agreement), the Pharmacovigilance Procedure, and the Guideline for the Performance of Delegated Obligations and Pharmacovigilance Activities in Ukraine. No missing information other than that specified in the non-compliance was found. This non-compliance had no negative impact on the pharmacovigilance system or the medicinal products, since all the above-mentioned "AAA" processes were actually performed by the QPPV. Such responsibility was defined in accordance with clause 4, clause 6, clause 8 of the "Contractual Document" (Agreement), as well as in the relevant procedural documents SOP "Process name 1," SOP "Process name 2."
2) During further assessment, it was found that, in the absence in the SOP of such items as the identification of information sources, the criteria determining the need to post/update information on the website, and the procedure for verifying the currency of information on the website, there is a risk that patients/website users do not receive up-to-date information on medicinal product safety. The safety information for all medicinal products posted on the company's website was retrospectively analyzed, and it was established that the information for eight medicinal products was out of date. |
| Corrective measure(s) |
| 1) Update the personal information of the LCPPV/deputy LCPPV, and include information on the duties of “AAA” for performing delegated obligations and pharmacovigilance activities in Ukraine.
1.1) Acquaint the QPPV/deputy QPPV with the updated PI against signature.
2) Updating/approval/training/implementation of the SOP "Procedure for Updating Information on Medicinal Products on the Company Website," version 02, including information on:
- criteria determining the need to post/update information on the website;
- identification of information sources;
- deadlines for updating information on the website;
- procedure for checking the relevance of information on the website.
2.1) Update of safety information for eight medicinal products on the company website. |
| Work result(s)
1) Updated PI KOVF
1.1) The QPPV/deputy QPPV was acquainted with the updated PI against signature
2) Updated SOP “Procedure for updating information on medicinal products on the company website” – version 02:
a) update/approval
b) training of responsible personnel
c) entry into force
2.1) Safety information for eight medicinal products updated on the company website |
Deadline(s)
1) 30.09.2022
1.1) 30.09.2022
2) to 30.11.2022
a) 31.10.2022
b) 29.11.2022
c) 30.11.2022
2.1) 15.08.2022 (completed) |
| Precautionary measure(s) |
1) Updating/approval/conducting training on/putting into effect an SOP “Process name” containing information on:
- involvement of the QPPV/employees of the Pharmacovigilance Department in the creation/updating of local SOPs of pharmacovigilance personnel;
- review/update of local procedural instructions (PIs) of pharmacovigilance personnel in case of changes in legislation, the “Contractual Document” (Agreement), changes in processes or structure in the company that require a review of the PIs.
2) Updating/approval/training/implementation of the SOP “Procedure for Creating and Updating Procedural Documents” with information on unscheduled review of pharmacovigilance procedural documents, for example in the event of changes in legislation, the “Contractual Document” (Agreement), or changes in processes or structure within the company that require review of the SOP. |
| Work result(s)
1) Updated SOP “Process name”
a) update/approval
b) training of responsible personnel
c) entry into force
2) Updated SOP “Procedure for creating and updating procedural documents
a) update/approval
b) training of responsible personnel
c) entry into force |
Deadline(s)
1) to 30.11.2022
a) 31.10.2022
b) 29.11.2022
c) 30.11.2022
2) to 31.10.2022
a) 30.09.2022
b) 30.10.2022
c) 31.10.2022 |
|
|
|
Example of incorrect completion by the applicant of the table based on the results of the pharmacovigilance system audit
| Result SN |
“Process name” |
| 1) The job descriptions of the QPPV/deputy QPPV (hereinafter – JD of the QPPV/deputy QPPV) do not document the responsibilities regarding "AAA" for performing the delegated obligations and pharmacovigilance activities in Ukraine, as stated in the "Contractual document" (Agreement).
2) The current procedural document SOP “Procedure for updating information on medicinal products on the company website” needs further work, as it does not contain information on:
- identification of information sources;
- criteria determining the need to post/update information on the website;
- procedure for checking the relevance of information on the website.
Regulatory references:
• Procedure for Conducting Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 29 January 2007 under No. 73/13340 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996)
• Standard “Guideline. Medicinal products. Good pharmacovigilance practice. ST-N MOZU 42-8.7:2015”, approved by order of the Ministry of Health of Ukraine of 25 March 2015 No. 267 as amended by changes approved by order of the Ministry of Health of Ukraine of 05 April 2018 No. 620 |
| Root cause analysis |
| 1) The PI of KOVF was analyzed and it was determined that an update is necessary.
2) The QPPV did not consider it necessary to detail the description of the process in the SOP. |
| Further evaluation |
| 1) The job description of the KOVF will be updated, and the duties of “AAA” will be added.
2) Not applied. |
| Corrective measure(s) |
| 1) Update PI KOVF.
2) Update the SOP “Procedure for Updating Information on Medicinal Products on the Company Website” to include information on the criteria that determine the need to post/update information on the website. |
| Work result(s)
1) Update PI KOVF.
2) Updated SOP “Procedure for updating information on medicinal products on the company website”. |
Deadline(s)
1) 30.09.2022
2) 30.11.2022 |
| Precautionary measure(s) |
| 1) Not applied.
2) Update the SOP “Procedure for updating information on medicinal products on the company website”. |
| Work result(s)
1) Not applied.
2) Updated SOP “Procedure for updating information on medicinal products on the company website”. |
Deadline(s)
1) not applied
2) 30.11.2022 |
|
|
|
