Bart’s Corner: PV Crises

Dec 09, 2014

Pharmacovigilance, Drug Safety and Regulatory Affairs Author & Expert

PV / Drug Safety Crises

This is a follow up to the previous posting on PV Stress Tests.

During every PV person’s career, a “PV crisis” will arise. PV “crises” can occur in clinical trials or during marketing and may be of varying degree and type; so let’s define them first.

Although the following are not always crises, often they are:

  • A product safety issue. This can be one or more unexpected SAEs and sometimes deaths which may or may not be related to the drug. This is a common scenario.
  • An unexpected FDA inspection either at your PV site or at an investigator’s site. EMA/EU inspections are usually announced and should not be crises; however, I’ve seen companies turn them into crises!
  • An FDA or other health agency Warning Letter or equivalent or an FDA 483. This may or may not be related to an earlier inspection or safety issue.
  • A possible criminal activity: counterfeiting or tampering.
  • A regulatory “request” from FDA or another health agency to stop a study, recall or withdraw a lot or a drug, suspension of sales.
  • Other governmental issues: a Congressional hearing or Advisory Committee on your drug or a class of drugs
  • A media issue: a safety matter goes viral, a celebrity pans (or praises) your drug or says it is useful for an unapproved indication, an investigative news report in a newspaper or on TV, a movie making your drug a “villain” (for example, the 1982 film “I’m Dancing As Fast As I Can” about Valium®). The manufacturer moved into “crisis mode”.
  • A legal issue such as a lawsuit.
  • Article(s) published in a medical journal suggesting a new safety issue, often written by a prestigious professor. This can then go viral.
  • Internal company issues: Budget cutbacks with personnel loss, computer or IT problems or malfunction; changes by another department touching on safety (e.g. the legal department wants to review and approve every MedWatch form before it is sent to FDA), misconduct (whether deliberate or innocent) by someone on a safety matter, for example, in clinical research or drug safety. This might involve suppressing or hiding an SAE or death.
  • Problems with business partners on safety issues: Failure to report SAEs to you, late cases, lack of communication, an audit or inspection of the partner (the audit may be known or, worse, unknown to you if the partner never told you), a regulatory issue or product withdrawal affecting the partner etc.
  • A merger or acquisition that changes your company’s responsibilities, product portfolio, SOPs, etc.

These are only some of the possible examples. As you can see, some are predictable to a degree (e.g. a Warning Letter after a bad inspection) and others are not. Some may be (to use the tennis term) “unforced errors” and others are beyond anyone’s control.

But however one arrives at a crisis point, the company and the PV department must be ready to act immediately to protect the public health and to resolve the safety issue as rapidly as possible.

Several things must be in place in the company in order to ensure that the risks to public health and the possible damage to the company are minimized.

  • A company process and commitment to respond rapidly and forcefully to any safety matter, whether a crisis or not, to minimize the public health harm and legitimately protect the company (in that order). This should be carefully thought out at the highest levels in the company in advance; it should not be done for the first time during the crisis.There may be one or multiple processes (SOPs) to handle various types of crises: manufacturing crises, regulatory crises, recalls & withdrawals, safety and pharmacovigilance issues, media “attacks” etc.Focusing on the PV crises, the procedures put in place should cover the following:

A leader to take charge 24/7. This person should be senior and empowered. He/she should have the mandate to convene the appropriate personnel to define, investigate and respond to the issue. This usually takes the form of a safety committee and, in fact, the senior safety committee that handles all other safety issues (e.g. labeling, stopping trials etc.) may be the committee designated to handle crises. This committee should be chaired by the leader noted above. Some companies will form an ad hoc committee either reporting to the safety committee or separate from it to handle the particular crisis.

The members should include: the head of drug safety, the head of regulatory, a legal representative, quality/compliance, a project manager (or someone to handle the administrative work), subject matter experts, business partners if appropriate, representatives from the company’s affiliate or subsidiary if they are the focus. If there is a GMP issue, a representative from manufacturing should be a member. A company expert on media/social media should also attend. Usually some database searches or other IT reports will be needed so an IT member should attend. This is not a complete list and the chair should designate additional members including external consultants or experts as needed. Commercial representatives (e.g. marketing and sales) may attend but it must be clear to all that the primary focus is on public health and safety and not commercial matters. Each representative attending the meeting should also be empowered and able to make decisions at the meeting rather than having to clear an action with his/her hierarchy.

An up-to-date list of all the needed personnel with 24/7 contact information.

A meeting should be called ASAP, with distant or traveling members attending by phone or webcast.

  • An SOP or procedural document covering crisis management should be put in place prior to a crisis to document this commitment and to define the procedures to be put in place. This should be realistic and sufficiently detailed to be put in use immediately. If you don’t have one now, create one.
  • Minutes of the meetings should be kept. They should note the issues, action steps and assignments. They should be prepared (or at least reviewed and approved) by legal.
  • Senior management should be briefed initially and frequently thereafter, usually by the chair of the committee, on the issues and actions.
  • FDA and other health agencies will almost certainly need to be contacted and interactions with these agencies should be carefully coordinated and a single point of contact designated though if it is a complex issue (e.g. GMP and PV) then more than one point of contact may be needed. However this is done, all communications with agencies must be documented. Promises made must be kept.
  • As noted, it may be necessary to employ external consultants, experts or attorneys to assist the company in the investigation and response. It may be necessary to expedite the company’s internal contract process to get them on board rapidly. This may require contacts with the contracts group as well as the finance department to get the needed funds for these activities.
  • A spokesman for external media contacts should be designated. This person should have a “cool head” and should have experience and training in dealing with the media. Similarly, if something goes viral on social media, the company must decide immediately on whether to respond and how to do so. Even if the issue does not go viral, attention must be paid to social media.
  • In PV matters, where a massive increase in SAEs occurs or if there is suddenly a need to expand the normal functions of the drug safety/pharmacovigilance department, it may be necessary to go to an external safety CRO for assistance in case handling, follow-up etc. Again it may be necessary to rapidly expedite the contracting process here.In other situations, it may be necessary to bring in either internal or external epidemiologists, toxicologists, subject matter experts etc.
  • All action items must be tracked and completed. The committee and the chair should remain active till the crisis is resolved. If the situation evolves into a more chronic response (e.g. a new study) this responsibility may be passed on to another group. But whatever is done, promises must not be allowed to fall through the cracks.

Every situation and “crisis” is different and there is no one-size-fits-all response. The company must put in place a mechanism to deal with the issue. It must be flexible enough to respond to changing events as occurs in “the fog of war” (if you will forgive the military analogy). Things change rapidly and the company’s responses must be cogent, ethical and aimed primarily at protecting the public health.

For the PV personnel involved, these episodes become subsequent “war stories” that will be recounted over the years!


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