Pharmacovigilance has always been considered a critical activity by almost all the key stake holders, associated with drugs, and its high place in organizational priorities hasnever beenquestioned. From time to time, episodes like thalidomide tragedy (1961) and cardiovascularrisks posed by COX 2 inhibitors (2005) , only add emphasis to this ever evolving medico-regulatorydiscipline.

Traditionally speaking, the science of pharmacovigilance has been a discipline more focused on the post marketing or post authorization period. As a part of 'Risk Management Tool' it hasnot only an important role to play inpatients' safety, but it has alsoassumed astronomical significance, to safeguard pharma industry againstpossible loss of revenue through damaging litigations & declining share value. However, as biological scienceshave evolved, pharmacovigilance has also become an integral part of new drug development process. The new regulations (E2E Pharmacovigilance Planning) require that, thewould be marketing authorization holders, submit, in the application dossier,a comprehensivereview of the safety profile of the new drug, and how the potential risks will be further investigated and / or minimized during lifecycle of medicines.

Spontaneous reporting and Periodic Safety Update Reports (PSURs) for the marketed products, form the backbone of the traditional, post marketing surveillance activities throughout the pharma world. US FDA's MedWatch forms & MHRA's 'Yellow Cards' have almost become synonyms with spontaneous reporting.While US FDA recommends voluntary spontaneous reporting of allserious suspected ADRs through Form 3500A,for health care professionals,it makes such reporting mandatory for the Marketing Authorization Holders (MAHs) and draws very stringent timelines & reporting requirements.

All other adverse events / reactions, which are not reported to regulators,in an expedited manner are included in periodic clinical trial reports (in case of pre-marketed development phase)and in PSURsfor marketed products.

A PSUR is "a formal, structured update of the worldwide safety experience for a registered medicinal product (per ICH E2C standards), prepared for submission to regulatory authorities at defined times post-authorization". The contents of a PSUR (as per EU requirements) are as follows;
1. Introduction
2. Worldwide market authorization status
3. Update of regulatory authority or Market Authorization Holder (MAH) actions taken for safety reasons
4. Changes to reference safety information
5. Patient exposure data (marketed use, clinical trials, post marketingstudies)
6. Presentation of individual case histories
7. Studies
8. Other information
9. Overall Safety Evaluation (R/B Analysis)
10. Conclusions
11. Appendices

The US FDA & EMEA, now have gone, a step beyond these well known current pharmacovigilance practices, by asking Marketing Authorisation Applicants (MAAs)to submit Pharmacovigilance Plan (as per ICH- E2E guidelines) as a part of a larger "Risk Management Programme" (RMP) during the approval process itself.[Article 8 (3)(ia) of Directive 2001/83/EC]. To assist MAAs& MAHs in complying withthe requirements the EMEA has published the 'Guidelines on risk management system. [EMEA/ CHMP/96268/2005] which incorporates the concepts of ICH-E2E guidelines. Hence Risk Management, (a proactive approach to the safety profile of a medicines, which is continuously updated throughout the life cycle ofthe product),is an important advance in the sphere of pharmacovigilance & would have great implications & impact on all the important stake holders in time to come.

The current amended Schedule Y of Drug & Cosmetic Act,has taken care of PSURs to some extent, but leaves a lot to be desired. There is still some ambiguity regarding PMS studies vis-à-vis PSURs. The provisions of the Schedule Y can be summarized a s follows:
1.Subsequent to approval of the product, 'New Drugs' should be closely monitored for their clinical safety once they are marketed. The applicants shall furnish Periodic Safety Update Reports (PSURs) in order to
.report all the relevant new information from appropriate sources
. relate these data to patient exposure
.summarize the market authorization status in different countries and any significant variations related to safety; and
. indicate whether changes should be made to product information in order to optimize the use of the product.
2. Ordinarily all dosage forms and formulations as well as indications for new drugs should be covered in one PSUR. Within the single PSUR separate presentations of data for different dosage forms, indications or separate population need to be given.
3. All relevant clinical and non-clinical safety data should cover only the period of the report (interval data). The PSURs shall be submitted every six months for the first two years after approval of the drug is granted to the applicant.For subsequent two years the PSURs need to be submitted annually. Licensing authority may extend the total duration of submission of PSURs if it is considered necessary in the interest of public health.PSURs due for a period must be submitted within 30 calendar days of the last day of the reporting period. However, all cases involving serious unexpected adverse reactions must be reported to the licensing authority within 15 days of initial receipt of the information by the applicant.If marketing of the new drug is delayed by the applicant after obtaining approval to market, such data will have to be provided on the deferred basis beginning from the time the new drug is marketed.
4. New studies specifically planned or conducted to examine a safety issue should be described in the PSURs.
5. A PSUR should be structured as follows:
(a) A title page stating: Periodic safety update report for the product, applicant's name, period covered by the report, date of approval of new drug, date of marketing of new drug anddate of reporting;
(b) Introduction
(c) Current worldwide market authorization status
(d) Update of actions taken for safety reasons
(e) Changes to reference safety information
(f) Estimated patient exposure
(g) Presentation of individual case histories
(h) Studies
(I) Other information
(j) Overall safety evaluation
(k) Conclusion
(l) Appendix providing material relating to indications, dosing, pharmacology and other related information

As evident from the details, the PSURs requirement, mandated by the amended Schedule Y is restricted to the category of new drugs alone and that too,for a period of initial 4 years post approval. But it's the poor spontaneous reporting system in India, which is matter of great concern. No pharma company can create a worthwhile PSUR comprising of it's own data, unless, a sincere effort is made to have a robust pharmacovigilance system in place to train the field force, prescribers (and the patients?) then monitor, capture, record, communicate & analyze the adverse events arising from the marketed products.Till such time, the Indian regulatory agency will have no option but to rely on their counterparts in the more developed nations, for decisions related to drug safety.
(The author is senior manager, Global Pharmacovigilance Dr.Reddy's Labs,Hyderabad)