The Department of Risk Management and Medicinal Information at the Israeli Ministry of Health has published, for the public comments, a draft update to procedure No. 6, titled “Reporting of Adverse Events and New Safety Information”. This represents a new stage in the evolution of the pharmacovigilance (PV) policy applicable to pharmaceutical companies in Israel. The publication of this draft should ostensibly be significant positive news, but a preliminary review of the published document raises concerns that the updated draft guideline is partial, ambiguous and not comprehensive.
Background on the Development of the Existing Regulatory Regime
Contrary to common practice, duties in the field of pharmacovigilance were first established in 1998 through Ministry of Health (MoH) guidelines, even before the PV arrangement was set in legislation. Only years later, in a 2013 amendment to the Pharmacists Regulations (Preparations), 1986, did the regulations define what “pharmacovigilance” is, and formally established the duties for Marketing Authorization Holders (MAH) to maintain a PV system for medicinal preparations. For illustration, only in 2013 was the requirement to staff the pharmacovigilance system with specifically trained professionals first established.
Even since the initial principles were enacted, the regulatory framework itself has undergone significant “evolution.” Although no direct updates have been made to the procedure since 2013, the MoH chose to update the procedure indirectly. In this context, in 2015, the Department of Risk Management and Medicinal Information published a document titled “Clarifications for QPPV of Registered Preparations Regarding Reporting of Adverse Events and New Safety Information.” In 2017, another amendment to the PV policy was formulated, this time through a document titled: “Q&A on Reporting Adverse Events and New Safety Information and Risk Management Plans.” In this way, the MoH has provided MAHs with necessary clarifications from time to time regarding questions that arose in relation to the practical implementation of the PV duties.
The PV policy in Israel, which was established in Procedure 6, was thus created, developed, and implemented in “small steps”, through a lengthy evolutionary process.
The Current Update Should Create Uniformity and Clarity
The result of the process described above is that Israel’s PV policy is based on a combination of different documents. Anyone seeking to know their duties in this substantive area must navigate between Procedure 6, clarification documents, and Q&A document, and formulate for themselves—based on combining these documents—the arrangement applicable to their specific product and case.
Regulation in this manner is not optimal and may create ambiguity regarding the binding regulatory framework. Therefore, the MoH did well in its decision to consolidate the various regulatory documents and unify them into Version 4 of Procedure 6, which is expected to come into effect on September 1, 2025. Ostensibly, the draft distributed for public comments should be seen as important and positive news. However, even a preliminary review of the formulated draft reveals that it is a partial and incomplete arrangement, which for some reason leaves various provisions already included in the current policy documents outside the document that purports to reflect the MoH’s comprehensive policy in the field of PV. Without being exhaustive, here are two examples of these important issues that for some reason were not included in the draft procedure:
- Reliance on reports from abroad – In the current version of Procedure 6, it was established that for preparations with a MAH/manufacturer abroad, reporting can be done through signals as received or identified by the MAH or manufacturer abroad after they have been evaluated by the company and assessed as possibly related to the drug marketed in Israel. For some reason, this rule, which has sound logic behind it, is not included in the distributed draft.
- Monitoring scientific literature – As part of the Q&A document from 2017, it was clarified that the literature review should be limited to articles related to the safety of drug treatment in humans only. Additionally, the literature review was supposed to be limited to cases involving a “signal” that requires regulatory action. These two requirements have been omitted from the draft, in a way that could potentially lead to a significant expansion of the literature search duty.
Against this background, it is important that QPPVs thoroughly examine the content of the draft to ensure that all arrangements that included in the series of documents through which the PV policy was applied are fully unified into the new arrangement. The publication of the draft also presents an opportunity to propose changes and additions to the MoH in order to align the arrangement practiced in Israel with those accepted by leading regulatory authorities.
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Dovev Apel, heads the Life-Science field at S. Horowitz & Co., is available to answer questions related to this provision and to prepare for its implications.
