Monday, 16 May 2022

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:

Organizers details:

Written by:
Dr.shraddha Bhange.
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Saturday, 18 December 2021

Signal Detection: Introduction

Signal detection is the most extensive and critical topic in PV. While it is almost impossible to cover it one simple blog, we can try to introduce it at least.

 Definitions: New potentially causal association, or a new aspect of a known association between an medicinal product and an event or set of related events which may require some action for ensuring patient safety. A signals may only be relevant for a particular medicinal product or a whole class of medicinal products.


Sources of Signal detection:


1. ICSRs 

2. Clinical trial data , Spontaneous data, Scientific literature

3. Experimental and/or non-clinical findings which has a significant impact on human exposure

4. Databases with larger datasets when the signal was detected from national or marketing authorization holder-specific databases (Eudravigilance)

5. Healthcare databases that may provide information on characteristics of exposed patients and medicines utilization patterns (VigiBase-WHO, FAERS)

6. Information from other regulatory authorities worldwide

Steps in Signal detection:

1.  Detection: Using signal sources , first step is to assess if there is signal.

2.            Validation : Once a signal is identified, validating it       with different methodologies, and assessing if a true causal link is present between the event and drug.

3.  Analysis and prioritization: Once we validate that a signal is indeed present , the next step is to analyze if the identified signal (event) is serious, severe, reversible, irreversible and its impact on public. A event that causes a irreversible damage or requires a very risky and expensive treatment obviously needs high prioritization. 

4.         Assessment and recommendation for action: Once we prioritise a signal, we need to ensure there is action taken to minimise the impact of signal. E.g. if a signal is identified as drug induced liver injury, then we may have to inform HCPs via USPI/ trainings to monitor liver enzymes of patients.


Examples of actions to be taken:


1.    Urgent Dear Health Care Professionals Communication warning of potentially increased risk of adrenal crisis during the swap over period, with the risk theoretically being highest in youngest patients, and those with least adrenal reserve or other comorbidities.

2.    An update to the reference safety information.

3.    An update to the EU RMP


  Written By:

Dr.Shraddha Bhange

Sunday, 5 December 2021

PADER-Periodic Adverse Drug Experience Reports

 What is PADER?

 Periodic Adverse Drug Experience Report (PADER/PAER) is aggregate safety reports required from MAH to be submitted consisting of ICSR submission and their analysis by FDA as per guidance 314.80 (c) and 600.80 (c) (2). 

Why is it needed?

 PADER serves the purpose of collating, updating, evaluating, and providing a summary of post-approval information of a product along with its benefit-risk profile evaluation.

 The key difference is a detailed analysis is not required as per PBRER/PSUR format. Only mention about labelling changes already performed are added. But the actual analysis done during the current PADER and if this data led to changes in labeling of product or if additional investigations are required for any of the new/existing risks mentioned for products is dealt separately and not mentioned. 

When is it needed?

 For the first three years, the company needs to submit the report quarterly and, thereafter, annually upon obtaining approval from the FDA.

 MAH must submit Quarterly PADER within 30 days of the close of the quarter beginning from first quarter from date of approval.

MAH must submit Annual report within 60 days of the anniversary date of approval of the application.

 Waiver not to submit PADER

 An MAH can take waiver from FDA and update the NDA listing and submit PBRER/PSUR instead of PADER in ICH regions.

 Key points for drafting PADER

 1.Ensure all the ICSR are already submitted during the review period (15 day reports), and their submission dates are entered in safety database. If any ICSR not submitted then MAH need to submit it ASAP and initiate CAPA as per internal process.

 2. The cases/ICSR that are going to be submitted as part of PADER are closed in safety database to generate their XML’s.

 3. The ICSR that needs description should be 15 day expedited cases along with their clinical significance. Narrative should be brief, with emphasis on data only about serious and unlisted event, hence avoid copy and paste of narratives. Company comments explaining MAH causality of case should be retained.

 4. Explain the 15 day expedited and other cases in brief manner and corelate their significance in terms of impact on benefit-risk profile of product.

 5. Attaching the recent USPI and describing a very briefly what were the changes in USPI made during review period. Adding any postmarking studies, regulatory actions and any new safety measures implemented in respective sections.


 Written By:

Dr.Shraddha Bhange

Sunday, 24 October 2021

DSUR (Developmental Safety Update Report)

 DSUR (Developmental Safety Update Report)

In an earlier blog by Dr. Shraddha Bhange, we learned about PSUR/PBRER. Today, we'll look at the other counterpart for this report, which is prepared while the product is still in development phase i.e. DSUR, which stands for Developmental Safety Update Report. We can also call it as a pre-marketing equivalent of a PSUR (Periodic Safety Update report).

Before we go to the core of content and format, first let’s understand what a DSUR is?

DSUR is an internationally harmonized, safety document which covers the safety summary of investigation products during their development or clinical trial phase. This means that all new drugs under development that are currently undergoing a clinical trial must submit a DSUR to the regulatory authorities.

Now you might be wondering, why do we come across DSURs for medicines which are already on the market. There will also be instances where a product is already on the market, but the sponsor/MAH (Marketing Authorization Holder/Pharma Company, wants to further evaluate the drug; for example, for a new dose, new formulation or a new indication that is not covered by the drugs approved marketing status. In that case, the sponsor must submit  DSUR until the clinical trials for a marketed drug are ongoing.

What are the objectives of a DSUR? The purpose of a DSUR is to provide a comprehensive annual analysis  of the safety summary collected during the clinical trial. You may consider the document as a communication to the regulators about adequate monitoring and evaluation of a safety profile of a drug under investigation.

What is the scope of products for a DSUR? A DSUR may be required for any of the following

-          Investigational drugs

-          Investigational Biologicals

-          Investigational Vaccines

-          Combination products under investigation.

What is DIBD?: - Before we discuss the frequency and duration, it is important to understand what a DIBD is.  DIBD is also known as – Developmental international Birthdate (DIBD) – it is the date of first authorization from a regulatory agency to the sponsor to conduct any clinical trial for an investigational product anywhere in the world.

How long is it to be submitted?- A DSUR is to be submitted as long as the clinical trial is ongoing. When submission of an annual report is no longer required in an individual country  or region, the sponsor should indicate that the final DSUR serves as the last annual for the investigational drug in that country or region.

What is the frequency of a DSUR submission?- Usually the DSUR is submitted annually (the frequency may vary occasionally as per national or regional regulatory requirement).  

 The first DSUR should have a data lock point which should be within a year of its DIBD.

Also note that the DSUR is to be submitted to the regulatory authorities within 60 calendar days after the DSUR data lock point.

What is the reference safety document for a DSUR? Unlike PSUR, in case of DSUR the IB i.e. the Investigators Brochure stands as a reference document for the DSUR report.  

The Format and Content is described in International Conference on Harmonization (ICH) guideline E2F.

Each section of DSUR is highlighted in the table below, along with a brief overview of what each section entails.



 Comment for ease of understanding

Part I

Title Page

 Information about company, author of DSUR, Reviewers , data period etc

Part II

Executive Summary

 Snapshot of DSUR , summary of risk-benefit of product



-          DIBD and Reporting period

-          Details of investigational drug- mechanism of action, therapeutic class, dose, route, and formulation, indication etc


Worldwide Marketing Authorization Status

-          Date of first approval

-          Indication(s), approved dose(s), and countries where approved, if applicable.


Actions Taken In the reporting interval for Safety Reasons

-          Significant safety related actions taken during the reporting period along with reasons for each action. e.g. Regulatory authorities requested hold on clinical trials, withdrawal of product etc


Changes to Reference Safety Information

  Significant safety-related changes to the Investigators Brochure OR USPI or other such RSI documents within the reporting period.    


Inventory of clinical trials ongoing and completed during the reporting period

-          Overview of the clinical trials ongoing and completed by the sponsor during the reporting period.



Estimated Cumulative Exposure

6.1 Cumulative Subject Exposure in the Development Programme

6.2 Patient Exposure from Marketing Experience

-          Sections 6.1 and 6.2 of the DSUR should provide information on cumulative exposure in clinical trials and the marketed setting, respectively.



Data in Line Listings and Summary Tabulations

7.1 Reference Information

7.2 Line Listings of Serious Adverse Reactions During the Reporting Period

7.3 Cumulative Summary Tabulations of Serious Adverse Events


This should present important clinical safety information through line listings (cumulative and reporting period)


Significant Findings from Clinical Trials during the Reporting Period

- 8.1 Completed Clinical Trials

- 8.2 Ongoing Clinical Trials

- 8.3 Long-term Follow-up

- 8.4 Other Therapeutic Use of Investigational Drug

- 8.5 New Safety Data Related to Combination Therapies

-          Each sub section should provide a brief summary of clinically important emerging efficacy and safety findings from clinical trial


Safety Findings from Non Interventional Studies

-          Relevant safety information from sponsored or co-sponsored non-interventional studies (e.g. observational studies, epidemiological studies, active surveillance programmes)


Other Clinical Trial/Study Safety Information

-          Relevant safety information from any other sponsored or co-sponsored clinical trial/study sources (e.g. results from pooled analyses or meta analyses of randomized clinical trials)


Safety Findings from Marketing Experience

-          Applicable in case investigational drug has been approved for marketing in any country

-          Should provide a summary of key safety findings that have arisen from marketing experience.


Nonclinical Data

-          Major safety findings from non-clinical in vivo and in vitro studies (e.g. carcinogenicity, reproduction or immunotoxicity studies) ongoing or completed during the reporting period.



-          New and significant findings, either published in the scientific literature or available as unpublished manuscripts, relevant to the investigational drug during the reporting period.


Other DSURs

-          In case, multiple DSURs are to be prepared for a single investigational drug, this section should summarise significant findings from other DSURs. .



Lack of Efficacy

-          Data indicating lack of efficacy for investigational drugs intended to treat serious or life-threatening illnesses (e.g. excess cardiovascular adverse events in a trial of a new antiplatelet drug for acute coronary syndromes)


Region-Specific Information

-          The information in this section can be used to comply with national or regional requirements and can be provided in appendices to the DSUR. 


Late-Breaking Information

-          Important safety findings that arise after the data lock point but while the DSUR is in preparation.  


Overall Safety Assessment

18.1. Evaluation of the Risks

 18.2 Benefit-risk Considerations


-          Concise, integrated evaluation of all new relevant clinical and non-clinical and epidemiological information obtained during the reporting period relative to the previous knowledge of the investigational drug. 


Summary of Important Risks

-          Concise, cumulative, issue-by-issue list of important identified and potential risks.



-          Changes to the previous knowledge or efficacy and safety since the last DSUR.

 To summarize, DSUR is a complex and analytical document that should be utilised to analyse risk and safety profile of product in an ongoing manner.


 1. FDA

2. EMA

All opinions are personal and does not constitute any relevance or data regarding authors/reviewers/Blog owner's employer.

Written By
By: Manisha Bhosale (MBBS,M.D.Pharmacology)
PV Professional since more than 10 years.

Coviewed By:
Dr.Shraddha Bhange