VII.B.6. Quality systems for PSURs at the level of marketing authorisation holders

Marketing authorisation holders should have in place structures and processes for the preparation, quality control, review and submission of PSURs including follow-up during and after their assessment. These structures and processes should be described by means of written policies and procedures in the marketing authorisation holder’s quality system (see Module I).

There are a number of areas in the pharmacovigilance process that can directly impact the quality of PSURs, some examples are case management of spontaneous and study reports, literature screening, signal management, additional pharmacovigilance and post-marketing research activities, procedures for integration of information on benefits and risks from all available data sources and maintenance of product information. The quality system should describe the links between the processes, the communication channels and the responsibilities with the aim of gathering all the relevant information for the production of PSURs. There should be documented procedures including quality control checks in place to check the accuracy and completeness of the data presented in the PSURs. In ensuring completeness of data, a documented template or plan for drawing data from various data sources could be developed. The importance of an integrated approach to benefit-risk evaluation should underpin processes and cross departmental input to PSUR preparation.

The PSUR should also contain the assessment of specific safety issues requested by competent authorities in accordance with agreed timelines and procedures. The marketing authorisation holder should have mechanisms in place to ensure that the requests made by competent authorities during the time of their PSUR assessment are properly addressed.

The provision of the data included in the summary tabulations (see VII.B.5.6.) should undergo source data verification against the marketing authorisation holder’s safety database to ensure accuracy of the number of events/reactions provided. The process for querying the safety database, the parameters used for the retrieval of the data and the quality control performed should be properly documented.

An appropriate quality system should be in place in order to avoid failure to comply with PSUR requirements such as:

• non-submission: complete non-submission of PSURs, submission outside the correct submission schedule or outside the correct time frames (without previous agreement with the competent authorities); • unjustified omission of information required by VII.B.5.;
• poor quality reports: poor documentation or insufficient information or evaluation provided to perform a thorough assessment of the new safety information, signals, risk evaluation, benefit evaluation and integrated benefit-risk analysis, misuse not highlighted, absence of use of standardised medical terminology (e.g. MedDRA) and inappropriate dismissal of cases with no reported risk factors in cumulative reviews;
• submission of a PSUR where previous requests from competent authorities have not been addressed;
• failure to provide an explicit evaluation of the risk-benefit balance of the medicinal product;
• failure to provide adequate proposals for the local authorised product information.

Any significant deviation from the procedures relating to the preparation or submission of PSURs should be documented and the appropriate corrective and preventive action should be taken. This documentation should be available at all times.

When marketing authorisation holders are involved in contractual arrangements (e.g. licensorlicensee), respective responsibilities for preparation and submission of the PSUR to the competent authorities should be clearly specified in the written agreement.

When the preparation of the PSUR is delegated to third parties, the marketing authorisation holder should ensure that they are subject to a quality system compliant with the current legislation. Explicit procedures and detailed agreements should exist between the marketing authorisation holder and third parties. The agreements may specifically detail the options to audit the PSUR preparation process.