Pharmacovigilance - questions and answers
Is the legal basis for pharmacovigilance inspections something new in the new Medicines Act?
No, the possibility of inspections was indicated in section 19 (4) and (5) of the Act No. 382 of 28 May 2003 amending the Medicines Act and the provisions have now been included in section 53 (4) and (5) of the new Medicines Act No. 1180 of 12 December 2005. The Danish Health and Medicines Authority has conducted inspections in this area in 2004 and 2005.
Which Executive Orders form the basis for inspections?
The current and most important Executive Orders forming the basis for inspections are the Danish Health and Medicines Authority's Executive Order No. 1214 of 7 December 2005 on the reporting of adverse drug reactions and periodic safety update reports etc. and the Ministry of the Interior and Health's Executive Order No. 1238 of 12 December 2005 on monitoring of adverse reactions to drugs.
How are companies singled out for inspection?
Inspections are carried out as spot checks and also if the Consumer Safety Division of the Danish Health and Medicines Authority has grounds for suspecting that a company has problems meeting deadlines for submission of periodic safety update reports or if such reports are inadequate.
A company can also be singled out for inspection if:
- its reporting of adverse events is not satisfactory
- several serious adverse events have been reported in respect of a medicinal product
- The Danish Health and Medicines Authority has received information from international monitoring.
What is inspected at an inspection?
At an inspection the quality management system is inspected, including the structure and revision of instructions and IT systems. Furthermore, the following is reviewed:
- organisational chart
- job descriptions for and training of staff
- documentation of adverse drug reactions
- compliance with deadlines for periodic safety update reports and the contents of such reports
- cooperation agreements
How many inspections have been conducted?
2004 and 2005 was a pilot phase for us, and a total of 17 companies have been inspected.
What have been the conclusions of the inspections?
Many companies have built up a system for the handling of pharmacovigilance, but there are also a few companies that do not have a well-working system in place.
What frequent deviations have been found on inspection of quality management systems?
- Lack of validation of IT systems
- Inadequate security of access to IT systems and only one check of entries
- No definition of time in instructions for the training of staff before the instructions come into force
What frequent deviations have been found on inspection relating to the issue "organisation and personnel"?
- Lack of training of employees and subsequent release for job functions.
- Sales staff do not make sure that information on adverse events is reported to the person responsible for pharmacovigilance.
- Inadequate job descriptions as to pharmacovigilance
What frequent deviations have been found on inspection relating to the issue "documentation of adverse drug reactions"?
- Lack of completion of reports on adverse drug reactions received by the companies from physicians, consumers, the Danish Health and Medicines Authority and others.
- No search for reports on adverse drug reactions in Danish medical literature
What frequent deviations have been found on inspection of the issue "periodic safety update reports (PSURs)"?
- PSURs had not been submitted in time
- The contents of PSURs was not in compliance with legislation, for instance there was no conclusion that adverse drug reactions could lead to changes in the summary of product characteristics
The Danish Health and Medicines Authority recommends that companies should prepare instructions for changes in summaries of product characteristics.
What frequent deviations have been found on inspection of the issue "cooperation agreements"?
The distribution of responsibilities between the local company and the parent company had not been determined.
What frequent deviations have been found on inspection relating into the issue "self-inspection"?
- Pharmacovigilance was not comprised by the instruction.
- Self-inspection had not been conducted in the pharmacovigilance area.
How does the Danish Health and Medicines Authority intend to select pharmacovigilance inspections?
Inspections of the companies' handling of pharmacovigilance will be carried out as spot checks. This may take place in connection with routine GMP or GDP inspections. An inspection will also be conducted if the Consumer Safety Division of the Danish Health and Medicines Authority has information that triggers an inspection. (See also the answer to question 3).
Companies are advised beforehand if the Danish Health and Medicines Authority wishes to inspect their handling of pharmacovigilance.