Summary of GVP (Guideline on good pharmacovigilance practices ) modules- GVP I

 

(GVP) Module I – Pharmacovigilance systems and their quality systems

Anyone who starts working in PV or is working in PV has to know the GVP modules sooner than later. Although this documents are freely available on internet, we have to refer them on ongoing basis as per our questions rather than just reading it once. Also, despite reading them, they do appear overwhelming as its daunting to extrapolate what exactly is requirement. Hence my attempt to summarize it below.

This module describes the quality management systems that should be part of pharmacovigilance process. The details provided act like guiding principles of establishing pharmacovigilance processes in terms of SOP, Infrastructure, Technology, People and Organizational level expectations. It also provides insights into what are measures that are expected to showcase if the PV process is working efficiently.

Summarizing a high level points from the module for revision below.

In a nutshell, the expectations are below

Ø  Having a PV process that lay down in written agreements that PV process are robust, effective and legally complaint i.e. SOP, Work instructions, user manuals, trainings materials and records

Ø  Having system in place that can communicate and ultimately prevent or treat identified adverse reaction in patients and general population via different channels to HCP/Patients etc

Ø  Having process to disseminate most correct and current product related safety information to consumers and patients

Ø  Having process in place to collect AE, analyze and take actions via signal, risk etc. to ultimately prevent, correct or treat AEs

The module also provides insights on how MAH can ensure the process is effective by establishing measurable outcomes wherever possible to check if the QMS is working.

Usually below are some standard outcomes that are used as KPI (Key performance indicators): (Extrapolated from guidelines)

•      Serious and non serious cases submitted on time
•       PBRER, DSUR or any other aggregate report format submitted on time
•       Any signals detected and there submission on time
•      Any new risk or change in risk that was identified and how was it communicated to HCPs, Patients and consumers 
•      Any recent audit finding and how they were handled - measures taken and the timelines meet
•      Any non compliance in process- how they are tracked and corrective and preventive actions implemented

An audits are scheduled on set frequency internally and or risk based audits can also be conducted.

Other important details described in the module are below

1. Quality cycle and its steps 

2. Organizational level requirement for each process to have objective clearly defined in terms of roles, responsibilities, timelines, frequency etc

3. Involvement of leadership in each aspect of process to ensure PV process is efficient to meet legal obligations

4. Objectives of PV system to ultimately fulfill obligations for patient safety

5. Requirements for technology's and infrastructure and how to integrate quality.

6. Having compliance and record management system

7. Having system to track any non compliances i.e. audit, inspection, CAPA etc

For detailed read on the link below: 

https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-module-i-pharmacovigilance-systems-and-their-quality-systems_en.pdf

Written by:

Dr.shraddha Bhange.

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Basics of ICSR (Case processing)-Revision

 

Basics of ICSR (Case processing)-Revision

No matter where you are in your Pharmacovigilance career, almost always your interview will start with ICSR processing questions ( till you specialize or diversify or reach senior leadership position). Although below are key basics but when you are in stressful situations of showcasing your knowledge to either a interviewer or a potential client on your understanding of ICSR it is challenging to address this questions and hence a quick skim of some tricky situations and questions helps.

1. 4 minimum criteria

  Tricky scenarios to look out for:

1. An article retrieved with your brand name product which does not specify any patient details but just "number of patients" - is it valid or invalid case and moreover how do you handle this situation.

2.  A case downloaded by an SDEA partner on behalf of MAH in another territory and forwarded 15 days late, is serious unlisted in their territory and you are responsible for only US territory- is it expedited case or not?

This are very grey area scenario which will be based on where the MAH has marketing authorization i.e. which regulations are applicable, FDA, GVP etc. And based on this regulations how the internal SOP and process are framed.

So in First scenario- you should first download full text if not already done, try to download the reference data from its original source to get patient details, if not do follow up. As conservative approach you could create a case for safety analysis at the time of signal detection. 

2. Decoding the regulations:

Regulatory guidance documents need to be referred on ongoing basis, this are not read once and done kind of study documents. So let go of notion or expectation that you will know all the guidance requirements on tip of your fingers. Each situation is different, but knowing where and which regulations to read is expected from professionals the least.

3. Source of ICSR

Yes we know there are two source of ICSR, Solicited and Unsolicited or Spontaneous. But there are variations which you need to be aware. An non company sponsored trials cannot be solicited unless there is agreement between MAH and third party for data sharing in that case- it will be either unsolicited or solicited but in category of "Other trials". This will depend on safety database you are using what options it has at the backend. Also Partner case, Health authority cases, Compassionate use etc. are also different categories in source of ICSR.

4. Data entry:

This includes seriousness, labelling, expectedness, coding of events and products (MedDRA &WHO-DD), Reportability and narrative.

4. a. Seriousness:  Knowing seriousness criteria and using it in real world are two different things. When do we use medically significant? It is not when no other criteria is fulfilled, but in fact when if event left untreated could have led to any of the other 5 criteria. IME or DME list is applicable only when MAH is in that territory or there is explicit mention in the process at SOP level to use this. However in absence of such documented process and clarity, its good to go with conservative approach of upgrading to serious when present in IME list.

4.b. Labelling : Knowing the correct document to use for labelling is the first step, its easier in most situations as there is only one IB, USPI or SmPC. 

• It is tricky when you have multiple versions of IB or different labelling documents in various territories. In this tricky situations rely on using the correct one based on date of occurrence, CCDS or any documented process for same. 
• It is also important to use the correct sections, e.g. in IB its section 6.5 Reference safety information or section for investigators to assess listedness.
• For the USPI – Use whole label to assess events Include Warnings and Precautions, Adverse Reactions ,Clinical Trials Experience, Post marketing Experience, Use in Specific Populations, Patient Counseling Information, Patient Leaflet  
• Overdose section only applies to events reported with overdose.

•        Generally, if an outcome (e.g., death) reported for adverse event exceeds the usual outcome for that adverse event as described in the labeling document, the associated event should be considered unlabeled.

•        Non-specific terms where the meaning of the adverse event can vary (e.g., feeling abnormal, drug intolerance) should be considered unlabeled, unless these terms are present in the labeling document. Additional information should be sought to obtain clarification.

 

4.c Causality : 

• In spontaneous cases it is implied causality meaning "related" by default however most MAH will leave it blank in event screen in database for both company and reporter unless explicitly stated. The causality can be described with evidence in company comments.
• In clinical trials, its binary causality meaning related and not related. For FDA, Sponsor causality drives reportability and for EMA the highest causality drives reportability. 

4.d Coding with medDRA and WHO-DD:

• MedDRA stands for : Medical Dictionary for Regulatory Activities. 
• It is used for coding events, patient history, indications, investigations, product issues, medication errors etc. Soft coding need to be avoided i.e. coding to lesser serious or severe term. 
• Abbreviations cannot be subsumed.
• Diagnosis cannot be subsumed based on signs and symptoms are reported.
• Specificity needs to be maintained
• Severity needs to be correctly captured i.e if high blood sugar is reported, Diabetes should not be coded.
• WHO-DD: A drug dictionary proves useful when tabulating medication usage because it classifies the same medication, often known by different names, into a single name. Its used to code suspect, cosuspect, conmeds, treatment medications etc.

4.e. Narrative writing

• Narratives are expected to be submitted for all cases reported expeditiously to any regulatory authority but are useful and should be made available when needed for other types of reports and purposes
• EU requires narrative for all cases, except non serious but MAH may choose to have narrative for all cases in their database
• Knowing what is most relevant for drug event pair and limiting narratives to that, e.g. history that is closer to event in duration or clinically to be included, conmeds that are most relevant to the drug and event. Lab tests that are repeated multiple times add no value but in that case records first and last day lab tests or those that are clinically relevant only.

5. Special case scenario

    Special Situations are non-standard medical conditions that provide valuable information (e.g. clinical and safety) about a medicinal product, even when they don’t occur in association with an adverse event or medical condition; therefore, should be recorded/ reported/ monitored.

•   Examples include abuse, misuse, medication errors, overdoes, off label use, product issues etc.​
• Knowing when to capture just special situations without AE is important, most MAH will database this case and then do follow up and some may use other database or category to track this.
• This data is required to be summarized in aggregate reports and signal detection 
• It provides insights in new indication, quality issue, product usage that impact quality or safety.

6. Medical review

Medical review is performed by trained safety physicians and is mandate for clinical trials cases.

• Writing company comment- refer to my blog on this topic for notes
• IND annual safety reporting for US FDA- will cover this topic in another blog. This is summary of index case (Serious unlisted and related by company/sponsor) and other similar cases in safety database. The FDA requires this analysis report for all SUSAR cases within 7 or 15 days to FDA, Investigators and ethics committee to provide most recent and evolving safety profile of investigational product.

7. Regulatory submissions:

Every regulatory authorities have their own timelines and its important to know the applicable timelines for the product you are handling and which RA is applicable. In general below are timelines that can be shared that are applicable commonly .

• Expedited safety reports with death or life threatening as seriousness criteria= As soon as possible but within 7 days of AE receipt date should be notified to all required stakeholders.
•  Expedited Safety Reports with other seriousness criteria = As soon as possible but within 15 days of AE receipt date should be notified to all required stakeholders.
•  CIOMS/MedWatch for manual submission to stakeholders.
• •Electronic reporting to HA database- XML/Manual via eudravigilance portal

 

Written by:

Dr.shraddha Bhange.

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What, how and who of PV for Freshers

 What, how and who of PV for Freshers

There are lot of freshers who approach industry experts to find them job in PV.  While its a good idea to begin with, but turning this idea into reality takes little bit more effort. So instead of just doing the traditional route of sending CV and message on Linkedin or whatsapp, add below steps to your plan as well.

Step 1 : What is it that you are applying for? What is PV?

Yes, we all can find definition of pharmacovigilance on number of websites, youtube video and that is a great start. But dig deeper. Read, understand and digest the definition in true sense . This will allow you to stand out because instead of traditional method of blurting the textbook definition you will be able to "REPRODUCE" definition as you understand not as its written in textbook.

So what is PV? 

"Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem."

1. It is collection of adverse event/side effects/ drug problems from patients, consumers and Healthcare professionals.

2. It is collection, monitoring and analysis of adverse events and their continuous monitoring to ensure the medicinal products in market are safe and effective for patients.

Step 2 How PV helps in patient safety?

The reported Adverse event data is analyzed to ensure the risks that are associated with the product/drug are manageable, treatable, reversible or preventable.

The adverse events collected are then translated into meaningful information for patients and consumers to make informed decisions regarding product safety and usage.

The information is also utilized to communicate to HCP (Doctors, Nurses etc) so they are aware of adverse events and how to  prescribe the product, educate patients on risks, prevent the risks or manage the risks. 

Step 3 Who reports the adverse events and where

1. All HCP can report adverse event (including pharmacist, nurse, lab technicians, doctors, students).
2. All patients and consumer can report too.
3. There is no legal obligation or action for reporting, neither there is any fee to be paid or earned.
4. Adverse events are reported to pharma companies toll free number, email id etc
5. Adverse events can also be reported to countries national regulatory authorities e.g. in India it is CDSCO, US it is FDA etc.
6. Reporting adverse event is free of cost, all reporting forms are available free on internet 

Step 4 Why you want to join PV?

Tricky question, try to answer it as genuine as possible but dont give too much philosophical answers as well.

1. The growth opportunities are great considering PV is mandatory through all stages of drug development to marketing.

2. The career is secure in terms of having mandatory regulations to pharma companies to have PV dept.

3. The ideology of helping patients by working and ensuring the medicinal product safety provides job satisfaction.

Thanks,

Shraddha

Speaker Opportunity at Pharmacovigilance Conference organised by Chandigarh College of Pharmacy

 It was an absolute pleasure to attend conference on pharmacovigilance and patient safety at Chandigarh College of pharmacy on occasion of National conference of pharmacovigilance and Clinical research. I owe this opportunity to Dr. Sridhar Yeshamaina, a well-known PV and clinical research expert and a one of the key person in my professional circle who motivates me to learn PV more every day.

 

I had privilege of talking about  Seriousness & Expectedness & Causality Assessment Criteria . I talked about how pharmacovigilance and drug pharmacovigilance from ICSR management, RMPs, risk minimization measures, signal detection impacts patient safety. The impact of seriousness , expectedness and causality is for the purpose of regulatory reporting but it actually impacts patients a lot. A serious unexpected and related case impacts patients health outcomes, cost and quality of life. 

 

National conference of pharmacovigilance and Clinical research 2022 is a conference which was organized by Chandigarh College of Pharmacy (CCP), Landran, Mohali, Punjab, India under the aegis of Chandigarh Group of Colleges (CGC), Landran it has many accolades such as Awarded as Best Private Pharmacy College in India in 2016). Chandigarh College of Pharmacy (CCP) is an affiliate of Chandigarh Group of Colleges (CGC) which was established under Sri Guru Ram Das Educational Society (Regd.) under the dynamic leadership of  SatnamSingh Sandhu, Chairman and Rashpal Singh Dhaliwal, President. CCP under the aegis of CGC is a premier institute in the northern region of India, setting benchmarks in the field of pharmaceutical sciences with its research.The institution was established in 2005.

The chief guests of honour were Prof Dulal Panda,  Director NIPER, Prof.Dr.Rajeshkumar Goel APTI President, Punjab branch, Rashpal Singh Dhaliwal, President CGC, Landarn. 

The conference was organised beautifully and i had most warm hospitality thanks to Organizing secretary

Dr. M.Arockia Babu, Director-Principal, Chandigarh college of pharmacy, landran.

 The esteemed speakers were Dr. Minaxi Khalera,Director-Clinical Research,AstraZeneca Pharma India Limited,Dr. Sridhar Yeshamaina,Senior General Manager - CDMA,Head - Global Pharmacovigilance,Clinical Development & Medical Affairs,Hetero, Hyderabad,Ms. Rajni Jha,Pharmaceutical Consultant,Pharmaceutical Regulatory Affairs and Quality,New Delhi,Dr. Vallabh Deshpande,HOD Pharmacovigilance Operations,Glenmark Pharmaceuticals Limited and many others.

This conference was attended by approx 200 members comprising students from all pharmacy courses and domain experts . It was a huge success as students from all nearby institutes were welcome too join. It gave them industry perspective as well in terms of job and entrepreneurship opportunities in this domain. It infused the importance of patient care through PV .

 

Topics of the conference were very interesting and were handpicked to make them relevant to Indian Pharmacovigilance scenario and the speakers chosen for the topics were absolute delight as they poured their expert knowledge about these topics.

More details about conference and topics an e-book available on website to download:https://www.ccpmohali.org/public/documents/abstract-book-2k22.pdf

Organizers details: https://www.ccpmohali.org/

Written by:

Dr.shraddha Bhange.

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Audits and Inspections in Pharmacovigilance

 Audits and Inspections in Pharmacovigilance

 Audits or Inspections word can catch anyone off guard, but at the same time its a huge learning opportunity for us to find deficiencies/gaps in process and how we handle our routine operations.

 
Being part of audit and inspections in the past, but also recognizing that I am not yet expert on this or far from expertise, I just figured learning by sharing would be a good revision to be audit/inspection ready.

 What are some basic readiness actions we can take from operations team (meaning the team that is actually handling pharmacovigilance on daily basis) and excluding the Quality Assurance (QA) team who is actually the owner/leader on audits/inspections. 

There is depth of information on type of audits, inspections, how to prepare for them , corrective action, inspection report etc, but I will focus only on actual easy and simple topics that are expected from any PV operations team member. Obviously, QA team and higher leadership roles in PV will have to know more than described herein. 

To give an example and put things in perspective, MHRA (Medicines & Healthcare products Regulatory Agency)  conducted 22 inspections in 1 year between April 2017 and March 2018, which took tremendous amount of time, money and resources of both, pharma companies and MHRA. During these inspections, MHRA identified 89 major findings in risk management plans, noncompliance in quality systems, analysis of safety data, and management of adverse drug reactions.

1) Document readiness :

All the document pertaining to processing of adverse drug reaction reports like receipt of the reports by fax, mail, hard copies or soft copies received via website, call center, sites, consumers/patients etc should be appropriately archived as per internal SOP (in line with HA requirements) and be available to be reproduced if requested by auditor or inspector.

 

If there is involvement of other vendor such as CRO (contract research organization)  or any other company to whom part of or all of PV is outsourced then both MAH (marketing authorization holder/pharma company)  a SDEA and additional document as needed on data archival should be clearly mentioned. Adverse drug reaction reports (SAE forms/ email form patient) etc are the most critical document as they contain personal information of patient protected udner various country specific laws and regulations, hence there storage and archival should be very clearly defined and followed.

 

All the other documents e.g. not limited to investigators brochure, CCDS, protocol, SmPC, labelling documents, DSUR,PBRER, clinical study reports etc should also be defined regarding there availability (common share file location -access restricted) and who is responsible for ensuring most recent versions are available to the team for reference and the update process should be defined. 

 

The SOP should clear enough to address who, what , how and when at company level so the process are robust. More details on this can be found  on GVP Module I.  All the team members processing the adverse events and handling PV should have training compliance and training matrix to showcase the SOP are followed.

 

2) Process consistency:

Process should be standardized to ensure all team members have clear defined role and responsibilities to handle data. e.g. The adverse drug reports received from reporter, consumer, investigators etc may not be completely consistent or documented, there has to be audit/inspection readiness document to prove that there are document to help in identifying and making this reports more coherent for PV practices. Hence how to to do follow up for missing information for adverse events, and what type of questions are critical for should be part of process.

3) PV professionals: 

There has to be clear documentation on handling of PV functions per requirements by local and National HA eligibility rules. The CV , JD (Job description), training records, training matrix should be clearly documented and regularly updates per requirement. Whenever required, only read and understood document may not be enough, but quiz or exam to ensure understanding should be implemented.

Many health authorities need medically qualified persons to handle PV functions of casualty assessment and medical narrative of adverse drug reaction reports. This has to be documented and also the training and required qualification to be updated.

 

4) PV practices:

There has to be clear documentation on each and every process. For e.g. mail communication with reporters, investigators patients, consumers to reproduce CRO/MAH attempt to have complete medical documentation of all adverse drug reactions (ADR) reports. All calls, e-mails etc between any PV professional at CRO or  MAH also documented to make sure each ADR/PV follow up attempts are tracked correctly.

 

The PV practices should also have assessment check points, if the process is effective and is being followed or not. Regular assessment of each SOP and process described in it should be planned and carried out. 

 

5) PV function readiness:

 Any request or actions from health or regulatory authorities in form of requests, questions, query, audit finding should be actioned and discussed across all PV team . Any action or root cause that is found to be due to other department should be communicated as such to them. Pharmacovigilance department should always be audit/Inspection ready, as it is department that concerns safety of patient and any finding or gap will impact all other departments and patients safety.

 

6) PV Database:

Knowledge on technical details on database used by MAH/CRO should be across PV team, and any data privacy measures, threats etc discussed and documented properly to ensure there are measures to avoid patient data leak etc. Appropraite team such as IT, Database vendors have to be involved to address this.

Thanks,

 Dr.shraddha

 

 

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 References: 

 

1.                https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-module-i-pharmacovigilance-systems-their-quality-systems_en.pdf

2.                https://www.gov.uk/government/organisations/medicines-and-healthcare-products-regulatory-agency

3.                https://www.pharmacovigilanceanalytics.com/opinion/pharmacovigilance-audits-inspections-and-pv-analytics/

4.                http://www.hpra.ie/homepage/medicines/regulatory-information/pharmacovigilance-and-post-authorisation-safety/pharmacovigilance-inspections

5.                https://www.gmp-compliance.org/gmp-news/pharmacovigilance-inspection-metrics

 

 

 

 

 

Writing Company assessment in pharmacovigilance

 

With changing times, it is said that we have lost a lot of our attention span and this if applied to our reading, makes us to read something quickly and come to conclusion. 

This is exactly what physicians, health authorities, responsible HCP (Healthcare Professionals) want to read when they read adverse event report preferably CIOMS/MedWatch. They just want to get idea regarding the reported adverse event and the suspect drug and what does the company's position is on this.

Medical assessment is known as company comment, sponsor comment, MAH comment and so on  but in this blog we will term it as medical assessment. The medical assessment or sponsor assessment or company comment is exactly the place where you will find this information.

What is medical assessment?

This is short description (generally not more than 4 to 5 sentences) regarding Sponsor's position with respect to the reported Adverse Event (AE) and Sponsor's suspected products and its relationship to AE in a very brief and conclusive way.

Who should write it?

Many Sponsors* and Regulatory authorities* prefer safety physician’s i.e certified medical doctors to  write it especially for Clinical Trials (CT) and Serious cases. However non serious and post marketing adverse event reports can be handled by experienced pharmacovigilance individuals who are not medical doctors per se but are HCP’s with proper training and expertise. In fact, regulatory guidelines are also not stringent regarding requirement of only medical doctors to write medical comment for all cases in PV , and same is being followed widely in industry.

Prerequisites for writing a comprehensive company comment:

     1.    Know the safety profile of drug- Refer to IB,RMP,SmPC,PIL .This helps to understand the mechanism of action and safety profile of suspect product in relation to the reported event.

 2.     Causality assessment- It is a topic, that will be explored in detail in another blog. However the important prerequisite is that causality assessment has to be done so you know your position as to is it a related or not to suspect product. This helps in writing sponsor assessment so that you know how and what to write. 

3.       Know the clinical presentation of the event, it is important to know the disease pathophysiology, risk factors etc so as to explain the event and correlation to drug.

4.     Know the time to onset/Latency (temporal relationship of the event and product).

5.      Knowing safety profile of other concomitant medications. This is not always very easy, especially in patients when conmeds are reported as none or many. The trick is first go by class of drugs and then download the SmPC/PIL/USPI of relevant drugs from company website/RA websites. (You can find such relevant websites on my previous blog)

What and how should it be framed?

Medical assessment is free text field in any Safety database used by Sponsor. Most Sponsors have a standard template to help drafting it.

Some common do’s are:

1.  Use full generic drug names (i.e. for the active ingredients) only; no abbreviations.

2.   If the case is not assessable due to poor documentation, describe what additional information is needed to determine causality. Ensure you send follow up for this missing information.

3.  If required, provide reference of case definitions/literature to support the assessment.

4.  Provide the statement regarding the current safety profile of drug in relation to current RSI and event (listedness).

Some common don’ts are:

1.   Be concise (e.g. do not repeat case demographics which are already mentioned in case narrative i.e age & sex, unless they contribute to the medical assessment).

2.    Avoid abbreviations including obvious one’s as well  e.g COPD,DM,URTI,HB etc .

3.   Do not include calendar dates but the number of days from exposure to event (e.g. 2 Days after treatment started) i.e latency; it is acceptable to give approximate dates (e.g. after about two months or 2 years when more appropriate).

4.    Avoid mentioning unsubstantiated or non-scientific sources to frame sentences.

5.    Avoid using very definitive and specific terms or personal opinions like it is highly impossible, not at all related etc.

6.    Avoid mentioning assessment for other company suspect products when not needed or when data is inconclusive.

Take home message : 

It is important to remember that the medical assessment should make medical and scientific sense and is standardized ( conveying  same meaning to every reader). It is company statement and the writer should remember that it can be challenged during audits/inspections.

*Sponsor/Marketing Authorization Holder/Manufacturer and RA/HA/NRA/CA (Regulatory Authorities/Health Authorities/National Regulatory Authority/Competent Authority) are used interchangeably for ease in blog but have different definition.

 Written by:

Dr.shraddha Bhange.

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Risk Management Plan (RMP)

 The most complicated and tedious document as per me in my PV career is RMP (Risk Management Plan). 

Who requests and why?

An RMP is requested for any medicinal product undergoing a authorisation application by various health agencies e.g. EMA, Japan etc.It is also an requirement to maintain one for medicinal product for its lifecycle.

What is RMP and how it helps?

An RMP serves as a planning document for assessing how the risks identified for a medicinal product would be managed.The RMP serves as document that can discuss about conducting PASS, additional pharmacovigilance activities required for certain risks that need monitoring. An MAH (Marketing Authorisation Holder) should start with dRMP (Developmental Risk Management Plan) once the clinical trials are initiated. Aggregate reports such a DSUR  serves as bridge/link for dRMP . The aggregate analysis done during each review period for DSUR will parallely help in identifying risks during the development of product.

The dRMP then can be drafted to become RMP.  RMP also serve as guidance for drafting SMPC/USPI/PI sections pertaining to safety.

Frequency or timelines of RMP?

RMP is a live document that has no DLP or no specific timelines for update once finalised/submitted. It should be updated on need basis, meaning whenever there is update with respect to any risks or risk minimisation measures identified while writing a aggregate reports, signal detection analysis, ICSR, Literature monitoring etc.

Template:

I have copied the RMP template below from EMA website (reference links below). Most of the health authorities do not have any standard template for RMP. Many MAH follow EU-RMP or REMS (FDA) template and is accepted.

Part I Product(s) overview 

Part II Safety specification 

Module SI Epidemiology of the indication(s) and target population(s) Module SII Non-clinical part of the safety specification 

Module SIII Clinical trial exposure 

Module SIV Populations not studied in clinical trials 

Module SV Post-authorisation experience 

Module SVI Additional EU requirements for the safety specification 

Module SVII Identified and potential risks  

Module SVIII Summary of the safety concerns 

Part III Pharmacovigilance plan (including post-authorisation safety studies)

Part IV Plans for post-authorisation efficacy studies 

Part V Risk minimisation measures (including evaluation of the effectiveness of  risk minimisation activities) 

Part VI Summary of the risk management plan 

Part VII Annexes 

Discussion about template:
The product specification would particularly be aligned with the product details which we can furnish form IB/CCDS/USPI . The part that is particularly tricky is where we need to mention identified ,potential risks and missing information (all definitions in GVP module V). Also it depends on which stage product is in, for a product that is yet to be approved, potential risks and missing information would be more. All other modules are self explanatory, the important one I can highlight is module SVII identified and potential risks which should explain each risk individually, the clinical details of it, diagnosis, treatment available, its severity and effect on population and how MAH will put forth the measures to minimize or prevent it.

It is important that MAH should monitor the outcome of each risk minimization measures that were included and implemented for risks.  If the outcomes or assessment of measures present need of change or additional measures for risks, the RMP should be updated and the measures should be immediately acted upon.

References:

https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/pharmacovigilance/risk-management/risk-management-plans

Written by:

Dr.shraddha Bhange.

Connect with me Via comments below or on linkedin. (I do not respond to Facebook messages)

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