Pharmacovigilance trainings: four basic considerations for establishment of training environment

Pharmacovigilance trainings: You love it or hate it, but can not ignore it 

Yes, you read it right! You love it or hate it but can not ignore it. If someone says WHY? The reason is quite clear and simple..it is regulatory requirement👮

Need to understand further refer my previous blog "Pharmacovigilance Trainings: a succinct summary from GVP Modules"

First thing we need to understand that pharmacovigilance trainings fall under pharmacovigilance quality systems (GVP Module I – Pharmacovigilance systems and their quality systems) (consider it serious as other pharmacovigilance process).  

Below mention four basic considerations will save you from future observation from audit (internal/external) or regulatory inspection. 

Let's discuss some of them one by one - 

1. All person involved in pharmacovigilance training should receive initial and follow-up continuing trainings whether new or existing employee. 

New Employee: - New employee should undergo all necessary trainings according to job role and training plan. 

Let's understand this with possible trainings case processor/data entry role - 

• Pharmacovigilance (PV) Trainings - Introduction of MedDRA and MedDRA coding, MedDRA  Term Selection: Points to Consider, Module VI – Collection, management and submission of reports of suspected adverse reactions to medicinal products, ICH Guidelines (ICH E2A, ICH E2B and E2D at least)
• Quality Perspective Trainings: GVP Module I- Pharmacovigilance systems and their quality system, Case level quality and Field level quality parameters or fields from the database, Organizational quality policy
• Audit and Inspection Specific Trainings: Module-III - Pharmacovigilance Inspections and Module IV- Pharmacovigilance Audits
• MAH/Organization specific controlled documents Trainings: Standard Operating Procedures (SOP), Work Instructions (WI), Job-Aid, Policy, Any other document deemed important by respective Marketing Authorization Holder (MAH) or organization.
• Human Resource Trainings (not direct relation with pharmacovigilance but essential to understand organization DNA and work environment)
• Database Trainings
• Trainings assessment methodology 

Existing Employee: 

• Training upon new introduction of controlled documents (SOP/WI/Job-Aid/Policy)
• Change or update in regulatory guidelines
• Change in PV database functionalities 
• Changes/Updates in Safety Data Exchange Agreements (SDEA)- MAH, Distributors and Manufacture type
• Trainings related to outcome of audit or findings of regulatory inspection
• Quality related re-trainings
• Periodic refresher trainings

2. Training plan and Training records- documented evidences that  proves person undergone sufficient relevant trainings which demonstrate competency for assigned job role

3.  Training of Non-Pharmacovigilance Persons - Any person who directly or indirectly involved in receipt of any type of safety information (which includes company's sales representative, receptionist, persons handling company's social media, HR & Admin, etc.)

4. If any organization uses training software or portal then relevant user manual or work instruction, audit trail, system generated outputs including compliance reports, user access management process, training allocation handling process is advisable to have documented.

In short, all staff should be appropriately trained with evidences of their training (theoretical and practical) in ongoing manner. 

     

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Pharmacovigilance Trainings: a succinct summary from GVP Modules

Training is integral part of success whether it is in sports or event any work. It is very much essential for establishment of quality systems. This is utmost true for quality systems in pharmacovigilance any setting like marketing authorization holders, competent authorities of Member States and the Agency.

Let's see what GVP Module I – Pharmacovigilance systems and their quality systems and other GVP Modules states about training in achieving quality systems in pharmacovigilance. 

1. A sufficient number of competent and appropriately qualified and trained personnel shall be available for the performance of pharmacovigilance activities [IR Art 10(1), Art 14(1)].
2. Ensuring that sufficient resource available and training provided.
3. All personnel involved in the performance of pharmacovigilance activities shall receive initial and continued training [IR Art 10(3), Art 14(2)]. For marketing authorization holders, this training shall relate to the roles and responsibilities of the personnel [IR Art 10(3)]. 
4. The organization shall keep training plans and records for documenting, maintaining and developing the competences of personnel [IR Art 10(3), Art 14(2)].
5. Training plans should be based on training needs assessment and should be subject to monitoring.
6. All staff members of the organization should receive and be able to seek information about what to do if they become aware of a safety concern.
7. There should be a process in place within the organization to check that training results in the appropriate levels of understanding and conduct of pharmacovigilance activities for the assigned tasks and responsibilities
8. Adequate training should also be considered by the organization for those staff members to whom no specific pharmacovigilance tasks and responsibilities have been assigned but whose activities may have an impact on the pharmacovigilance system or the conduct of pharmacovigilance. Such activities include but are not limited to those related to clinical trials, technical product complaints, medical information, terminologies, sales and marketing, regulatory affairs, legal affairs and audits.
9. Appropriate instructions on the processes to be used in case of urgency, including business continuity , shall be provided by the organization to their personnel [IR Art 10(4), Art 14(3)].
10.  Training should support continuous improvement of relevant skills, the application of scientific progress and professional development. 
11. The quality systems shall be documented by training plan and records. 
12. Training plans and records shall be kept and made available for audit and inspection [IR Art 10(3), Art 14(2)].
13. In scenario where QPPV has not completed basic medical training in accordance with Article 24 of Directive 2005/36/EC, the marketing authorization holder shall ensure that the QPPV is assisted by a medically trained person (i.e. in accordance with Article 24 of Directive 2005/36/EC) and this assistance shall be duly documented [IR Art 10(1)].
14. The applicant or marketing authorization holder should provide the QPPV with training in relation to its pharmacovigilance system. Consideration should be given to additional training, as needed, of the QPPV in the medicinal products covered by the pharmacovigilance system.

Module II – Pharmacovigilance system master file (Rev 2)

1. Staff should be appropriately trained for performing pharmacovigilance related activities and this includes not only staff within pharmacovigilance departments but also any individual that may receive safety reports.
2. A summary description of the training concept, including a reference to the location training files

Module III – Pharmacovigilance inspections (Rev 1)

1. Quality and adequacy of training, qualification and experience of staff during routine pharmacovigilance inspection
2. Training and experience should be documented individually and evaluated according to the requirements of the applicable quality system of the concerned competent authority.

Module IV – Pharmacovigilance audits (Rev 1)  

1. Under strategic level audit planning risk to availability of adequately trained and experienced pharmacovigilance staff (e.g. due to significant turn-over of staff, deficiencies in training processes, re-organisation, increase in volumes of work) also being considered.
2. The proficiency of audit team members requires a combination of education, work experience and training

Module VI – Collection, management and submission of reports of suspected adverse reactions to medicinal products (Rev 2)

1. Staff directly performing pharmacovigilance activities should be appropriately trained in applicable pharmacovigilance legislation and guidelines, in addition to specific training in report processing activities for which they are responsible and/or undertake
2. Data entry staff should be instructed in the use of the appropriate standards and terminologies, and their proficiency confirmed for EU guidance on training of personnel for pharmacovigilance
3.  Other personnel who may receive or process safety reports (e.g. clinical development, sales, medical information, legal, quality control) should be trained in adverse events/reactions collection and submission to the pharmacovigilance department in accordance with internal policies and procedures.
4. It is recognised that literature search results are a surrogate for the actual article. Therefore, it is expected that the person reviewing the results of a search is trained to identify the articles of relevance. This may be an information professional trained in pharmacovigilance or a pharmacovigilance professional with knowledge of the database used. 

Module VII – Periodic safety update report (Rev 1)

1. For all organizations, it is the responsibility of the person responsible for the pharmacovigilance system to ensure that the personnel, including pharmacovigilance, medical and quality personnel involved in the preparation, review, quality control, submission and assessment of PSURs are adequately qualified, experienced and trained according to the applicable guidelines (e.g. ICH E2C(R2) and this GVP Module VII). 
2. When appropriate, specific training for the different processes, tasks and responsibilities relating to the PSUR should be in place. 
3. Training to update knowledge and skills should also take place as necessary. 
4. Training should cover legislation, guidelines, scientific evaluation and written procedures related to the PSUR process. 
5. Training records should demonstrate that the relevant training was delivered prior to performing PSUR-related activities. 

Explanatory Note to GVP Module VII, Revision 3

Marketing authorisation holders (MAHs) may consider training on ICH E2C (R2) guideline and the ICH E2C Questions and Answers (Q&A) developed by the ICH-E2C (R2) Implementation Working Group (IWG).

Module VIII – Post-authorisation safety studies (Rev 3) 

1. For studies that are funded by a marketing authorization holder, including studies developed, conducted or analysed fully or partially by investigators who are not employees of the marketing authorization holder, the marketing authorization holder should ensure that the investigators are qualified by education, training and experience to perform their tasks.

Module IX – Signal management (Rev 1)

1.  Each organization should ensure that staff members are specifically trained in signal management activities in accordance with their roles and responsibilities
2. Relevant staff members within competent authorities and marketing authorization holders should familiarise themselves with the guidance and training materials on EudraVigilance outputs made available online by the Agency and the training should be documented in line with the organization's internal procedures

In short, each individual or team should be properly qualified and trained to perform designated pharmacovigilance activities (any). There should be provision on initial and ongoing training along with training plan and training documentation. Other personnel who may receive safety information (e.g. clinical development, sales, medical information, legal, quality control) should be trained in adverse events/reactions collection and submission to the pharmacovigilance department in accordance with internal policies and procedures. This also apply to members from health authority and investigators involved in clinical trials and safety studies.

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PHARMACOVIGILANCE TRAINING Is Crucial To Your Business. Learn Why!

Pharmacovigilance Training is Crucial to Business.

Yes! You have read it right.

Pharmacovigilance training is crucial for your business better than any other PV activity. Training is one of the crucial components for running the business however, it gets neglected many times. Pharmaceutical companies or Contract Research Organizations (CRO) are set up pharmacovigilance training departments and develop some training modules for their employees and give self consolation that they have set up PV training as per recommendation from the Good Pharmacovigilance Practice modules (GVP).

GVP Module I – Pharmacovigilance systems and their quality systems emphasize the importance of PV training by mentioning a few of the following recommendations-

1. A sufficient number of competent and appropriately qualified and trained personnel shall be available for the performance of pharmacovigilance activities [IR Art 10(1), Art 14(1)].
2. The organization should ensure that adequate resources are available and that training is provided.
3. All personnel involved in the performance of pharmacovigilance activities shall receive initial and continued training [IR Art 10(3), Art 14(2)].
4. For marketing authorization holders, this training shall relate to the roles and responsibilities of the personnel [IR Art 10(3)].
5. Training plans should be based on training needs assessment and should be subject to monitoring.
6. The organization shall keep training plans and records for documenting, maintaining, and developing the competencies of personnel [IR Art 10(3), Art 14(2)].
7. Training plans and records shall be kept and made available for audit and inspection [IR Art 10(3), Art 14(2)].
8. The applicant or marketing authorization holder should provide the QPPV with training in relation to its pharmacovigilance system, which is appropriate for the role prior to the QPPV taking up the position and which is appropriately documented
9. Where the QPPV has not completed basic medical training in accordance with Article 24 of Directive 2005/36/EC, the marketing authorization holder shall ensure that the QPPV is assisted by a medically trained person (i.e. in accordance with Article 24 of Directive 2005/36/EC) and this assistance shall be duly documented [IR Art 10(1)].
10. Adequate training should also be considered by the organization for those staff members to whom no specific pharmacovigilance tasks and responsibilities. 

In the majority of the organizations, the skeleton structure of training are as follow- 

• Induction Training - Self-explanatory- Given at the time of induction
• Ongoing Training - Issue of new controlled documents (i.e. SOP, Work Instruction (WI), Job-Aid) or Revision of existing controlled documents
• Refresher Training - Periodic Training for controlled documents
• Adhoc Training - As an when it is needed. Publication of new regulatory guidelines or training imparted as a part of a regulatory inspection or findings from audit or inspection.

Provision of pharmacovigilance activity is one of the mandatory requirements to obtain marketing authorization in certain countries. After getting marketing authorization, an organization should continue to monitor the benefit-risk profile of the molecule. Trained pharmacovigilance professionals are required to carry out PV activity.

According to GVP, training shall relate to the roles and responsibilities of the personnel. However, many organizations failed to identify training requirements according to job-role which might lead to delay or failure in PV deliverables in terms of quality and quantity. 

Let understand this with the ICSR example- 

Let us assume if any organization processed 220 Individual Case Safety Report (ICSR)/cases per month by 3 persons (Data Entry, Quality Review, and Medical Review). We can say that 10 cases are processed per day with 48 mins of average processing time (considering 480mins per day work and 22 working days). 

If we identify training gaps and planed targeted training and can able to reduce 20% (9.6 mins) of single case processing time. Then we can have 38.4 mins of average processing time and the same team can contribute 12.5 cases per day (instead of the previous 10 cases). That means we now have revised productivity of 275 cases per month i.e. ~ 25% rise compared to the previous month. 

If the same example we go for higher processing time then productivity falls significantly.

If we extrapolate this with the large numbers then it significantly impacts our work efficiency and that leads to business. 

This can be applied to the quality part also...In a general sense, data entry performed by a trained data entry person has a low or minimal error which leads to completion of quality review and medical review in a shorter time and ultimately productivity boost up and business also.

The training concept can be applied to other pharmacovigilance functions like literature review, aggregate reports, signal detection activities, etc. 

Once the system improves, then we can have no or minor findings in audits and inspections. Ultimately, It is a WIN-WIN situation for any organization by strengthening training culture and periodic assessment of the effectiveness of training. 

Signing Off. 

Thank you.😊

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Updated MHRA Guidance on the PSMF for products authorized in UK

                                                                  MHRA

From 1 January 2021, for medicines authorized in Great Britain, Marketing Authorization Holder (MAH) holders must maintain PSMF that described the pharmacovigilance system for UK authorized products.

• The PSMF must describe the global pharmacovigilance system and reflect the global availability of safety information for UK authorized products.
• MAH need to make sure that every pharmacovigilance system covering UK authorized products has been assigned a unique PSMF number by the MHRA.
• A UK PSMF number can be requested via the MHRA Submissions Portal from 1 January 2021.
• A UK PSMF number can be requested via the MHRASubmissions Portal from 1 January 2021.
• Single request for UK PSMF number should be submitted to MHRA, where the pharmacovigilance system is shared by several MAHs.

• For MAs that are specific to Great Britain: PSMF must be accessible electronically at the same point in the UK from which the reports of suspected adverse reactions referred to in regulation 187 of the HMRs are accessible.

For MAs that are specific to Great Britain, legal requirements concerning the format and content of the PSMF are outlined in Part 1 of Schedule 12A of HMR, which mirrors Chapter I of CIR. 

• For MAs that cover the whole of the UK or are specific to Northern Ireland: the PSMF must be located either at the site in the European Union, where the main pharmacovigilance activities are performed or at the site where the QPPV operates, in accordance with Article 7(1) of the CIR. The PSMF must be accessible electronically at the same point in the UK from which the reports of suspected adverse reactions referred to in regulation 187 of the HMRs are accessible.

For MAs that cover the whole of the UK or are specific to Northern Ireland, the legal requirements concerning the format and content of the PSMF that are outlined in Chapter I of CIR will remain unchanged.

As the legal requirements concerning PSMF format and content are identical for MAs that cover the whole of the UK and Northern Ireland, and those that are specific to Great Britain, a single PSMF can be used for all UK authorized products.

Source💬: MHRA- www.gov.uk 

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MHRA Submission: The Role of Initial Company Administrator

The UK has left the EU, and the transition period after Brexit comes to an end this year. From 1 January 2021, for medicines authorized in Great Britain, Marketing Authorization Holder (MAH), will be required to submit pharmacovigilance data to the MHRA, according to GB requirements.

MHRA will require following submissions via the new MHRA Gateway or/ICSR Submissions portal.

• All pharmaceutical companies involved in making medicines regulatory submissions and vigilance activities
• All medicines clinical trial sponsors wishing to make clinical trial submissions (Initial Applications, Substantial Amendments, End of Trial Notifications and Developmental Safety Update Reports (DSURs)) to the Agency
• E-cigarette producers
• Brokers of medicinal products·

The first person in an organization who completes the registration process will become the initial company administrator.

Factors to be considered for initial company administrator-

1. 👉Smaller Organizations- a company administrator may also be responsible for making submissions or managing a team who will make submissions. It is recommended that each organization has more than one company administrator.

2. 👉Larger Organizations – may have different teams or departments who will be doing submission via MHRA Submission Portal like regulatory affairs, pharmacovigilance units, clinical trials teams etc. MAH need to carefully consider who is best in organizations for initial company administrator. This person will be responsible for adding further company administrators.

 A difference between Company Administrator and User

 👮A company Administrator: -

• A company administrator has the ability to add, edit and disable other users.
• A company administrator will also be able to see records of submissions made by users.
• A company administrator also has the ability to register multiple companies under their account.
• The initial company administrator will have the same permissions as any subsequent company administrators. However, they will be responsible for completing the user access steps for the organization and setting up the first set of additional company administrators and users.
• There are no limits to the number of company administrators

 👷A User:

• A user cannot add other users and can only make submissions for the organization they are registered to.
• A user will not see records of submissions made by other users.
• They can be added to multiple legal entities if required.

Note: if adding more than 5 users at a time, the changes will be made but you will be redirected to the homepage rather than the “user maintenance” page. To confirm that your new users have been added, simply navigate back to the “user maintenance” page.

Source: MHRA- www. gov. uk

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How to gain access for performing submissions to the MHRA from 1 January 2021

 

The following groups will need to take access to MHRA Submissions in order to start submissions from 1 January 2021:

• All pharmaceutical companies involved in making medicines regulatory submissions and vigilance activities
• All medicines clinical trial sponsors wishing to make clinical trial submissions (Initial Applications, Substantial Amendments, End of Trial Notifications and Developmental Safety Update Reports (DSURs)) to the Agency
• E-cigarette producers
• Brokers of medicinal products

Gaining access to MHRA submission can be divided into three parts –

• User registration – the end to end process for adding an initial company administrator
• Add a new user – add an internal colleague as a user or company administrator
• Add a new external user – add a third-party consultant/consultancy as a user or company administrator

Prerequisite points💬 –

• The first Person In any organization who completes the registration process will become the first responsible administrator. Hence it is advisable that right person with appropriate consensus/permission becomes company administrator (registering as company administrator without permission could cause unnecessary confusion and delay to the company’s operational activities.
• Access of 5-digit company number(s) if any organization has previously submitted to the MHRA. (If you have not submitted to the MHRA, please email reference.data@mhra.gov.uk as you will need to register as a new company prior to beginning this process).
• All third-party consultants/consultancies have their own 5-digit company number and have registered for MHRA Submissions using that number.         

New Users

New users can straightway reach to MHRA account request page via the following link-

https://mhrabpm.appiancloud.com/suite/plugins/servlet/registration

Source: MHRA- www.gov.uk

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