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Many more health agencies are now doing pharmacovigilance inspections compared to years gone by. There are many reasons for this including the obvious ones of protecting the public health and ensuring that the company is following the laws, regulations and (unofficially) best practices. Other, less obvious reasons include generating fees (many agencies though not FDA charge the companies they inspect a pretty penny for inspections), and politics.

It is sometimes hard to know what will be cited as deficiencies or observations. Of course, one must follow the regulations but in many cases the regulations are obscure. The EU regulations (Good Pharmacovigilance Guidelines) are rather detailed whereas the US FDA regulations are less so. Canada falls somewhere in the middle in my view.

In February 2013 Health Canada’s Health Products and Food Branch Inspectorate released an interesting document entitled “Risk Classification of Good Pharmacovigilance (GVP) Observations” GUI-0063. See https://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/gui-0063_gvp-eng.php In this document Health Canada (HC) gives details on what risks they look for and how they classify them. Although this is limited to Canada, the contents are very generalizable to inspections done by all agencies. So for that reason we will go through this. Such clarity is not found in information supplied by other agencies around the world.

Firstly, HC will assign an overall rating to a company following an inspection:

Compliant (C) – “… the regulated party has demonstrated that the activities it conducts are in compliance with the Food and Drugs Act and its associated Regulations. A “C” rating does not mean that there are no observations or corrective actions required.”

Non-Compliant (NC) – “…the regulated party has not demonstrated that the activities it conducts are in compliance with the Food and Drugs Act and its associated Regulations.”

Note that there can be small observations found at an HP audit and corrective actions (CAPAs) required but that the company can still get an overall C rating.

Next HC describes risk ratings which is the “meat” of this document. These ratings are detailed in Appendix B of the document. A summary outline is presented below. See the document for more details:

Risk 1 (Critical) Observations:

Definition: “A situation that may produce an immediate or latent health risk as a result of the absence of drug safety information. Observations that involve fraud, misrepresentation are… are also considered critical.”

Comment: Note that there are not too many critical findings. As in the EU and US, expedited reporting that is not done is a critical observation as are changes in the benefit risk assessment that are not reported. Lack of record keeping or the inability to produce records are also critical findings. Note that periodic reporting is not mentioned here because, interestingly, HC does not require periodic reporting for all drugs as the FDA and EU do. They are submitted only upon request.

Definition: A situation of incomplete drug safety information that may result in a latent health risk.


Comment: Lots of major observations which are fairly consistent with FDA and the EU. Poor quality, bad records, missing records, non-validated computer systems, no or poor signal detection, literature searches, SOPs, bad data security, using out of date labeling, training, follow up, product complaint procedures, archiving, ASRs. Also having unqualified people doing PV, late cases, poor coding etc.

HC also reserves the right to upgrade a major to a critical finding.

Risk 3 (Other/Minor) Observations:

No real surprises here.

Summary & Conclusions

This is an excellent document in which Health Canada spells out the actual and detailed requirements of what must be in place for pharmacovigilance to get a “compliant” rating. This is entirely consistent with the FDA and EU and the observations they make at inspections. Similar requirements can be gleaned from public documents available from FDA, the EU and member states (particularly the MHRA).

HC is to be commended for clearly publishing the rules up front. There should be no surprises when an HC inspector finds some of these issues and cites them in the inspection report.

The message here to companies is that this is the necessary minimum that needs to be in place for pharmacovigilance, whether in-sourced or out-sourced, whether domestic or global. Although this is primarily written for post-approval (authorized) drugs, it can equally apply to the principles, procedures and requirements that must be in place for clinical trial pharmacovigilance and drug safety with various additions and subtractions for items that apply in that setting.

This checklist should be used by internal and external quality and compliance auditors when doing PV gap analyses, audits and mock inspections.

We have been warned.

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