|
Even though a significant number of pharmaceutical companies have stepped up efforts to put in place pharmacovigilance (PV) system at their sites and appoint pharmacovigilance officer in-charge (PvOI), as mandated by the Union health ministry through a March 2016 notification, most of them are yet to comply with the PV guidance document that came into effect from January this year, in the absence of regulatory mandate as well as due to lack of clarity in certain provisions of the guidelines.
This PV guidance document has been released for the first time by the government of India for pharmaceutical industries aiming to set up and ensure an effective PV system at their site as per amendment in the drugs & cosmetics rules, 1945, schedule Y vide gazette notification G.S.R. 32 (E) published on March 8, 2016.
“It has been six months since the PV guidance document for marketing authorization holders (MAHs) came into force, but the compliance of PV guidance document is at its nascent stage in the country due to lack of regulatory mandate. The government should take steps to incorporate the PV guidance document in drugs and cosmetics act to ensure its cent percent compliance by drug industry,” said Dr J Vijay Venkatraman, a PV expert and managing director and CEO of Oviya MedSafe. Around 200 companies have submitted individual case safety reports (ICSRs) to Pharmacovigilance Programme of India (PvPI) in April 2018 as per PvPI newsletter.
A number of companies are facing practical difficulty to comply with certain provisions of the guidelines.
There are six modules in the guidance document. As per module two of the document, all ICSRs received by MAHs are mandated to be submitted to PvPI in XML-E2B format, it implies the indispensable need for an electronic pharmacovigilance database. The MAH is required to code ADRs using a dictionary but no specific dictionary has been recommended, said Venkatraman.
However, indications of the suspected and concomitant drugs must be coded using the latest version of the International Classification of Diseases, which allows room for redundancy. The document lists the WHO-UMC causality assessment scale as the preferred tool for causality assessment. It also states that causality assessment by MAHs is mandatory for new drugs. The document establishes the timelines of reporting to PvPI as 15 days for serious adverse events/ADRs and 30 days for non-serious adverse events/ADRs. However, it is not clear on whether serious adverse events/ADRs need to be reported to both the regulatory authority and PvPI or if reporting to one of them will suffice. In addition, the requirement for serious unexpected ADRs to be reported to the licensing authority (which may be the CDSCO or any of the state drug licensing authorities) paves way for ambiguity due to opening of multiple reporting channels. Lack of efficacy cases and medication errors must also be reported, he added.
As per module three, periodic safety update reports (PSURs) should be submitted within 30 days of the last day of the reporting period. All dosage forms and formulations as well as indications for new drugs should be covered in a single PSUR, with separate presentations of data given for these special situations. The PSUR must provide separate line listings of ICSRs received from India and from the rest of the world.
The drug industry has found it challenging to report PSURs in 30 days in the wake of voluminous data. The government should give companies at least 60-90 days to report PSURs in line with global practice. If companies have no ICSR, preparing PSUR is comparatively easier but when quite a few ICSRs are there, it is difficult to complete the PSUR in a month, he said.
While module six states that the regulatory authority shall approve every risk management plan (RMP) for every product, it is not clear whether this condition applies to products already in the market or only to products that would be introduced prospectively. Moreover, the format in which a RMP has to be prepared and submitted by a MAH has not been provided.
There is no dedicated module for signal detection despite it being referred to in the modules on pharmacovigilance system master file (PvMF) and PSURs, he opined.
Talking about measures to enhance pharma industry’s compliance with PV regulations, the PV expert said, “Healthcare professionals should come forward to report ADRs which will in turn spike companies' ICSR submissions to PvPI. As of now PvPI is educating and guiding industry on PV guidelines to ensure that companies have an effective PV system and they comply with PV regulations and requirements of the CDSCO. It is anticipated that PvPI would inspect pharma companies in the future to make sure that they comply with the applicable PV obligations.”
|