Medical Device Enforcement and Quality Report

In light of recent criticism of FDA’s oversight of medical devices, it is curious why FDA did not release a report touting the success of its enforcement activities with the same fanfare as its report on its plan to modernize the 510(k) program, which we reported on here. The Medical Device Enforcement and Quality Report (Report), available here, claims FDA’s increased inspections have led to improved compliance by industry.
— Read on www.fdalawblog.net/2018/12/medical-device-enforcement-and-quality-report/

Change Management – Post Change Evaluation and Action

In “Change Management – Post Change Evaluation and Action” John Hunter (of CuriousCat) writes a nice post on the The W. Edwards Deming Institute Blog on linking change management to the PDSA (PDCA) lifecycle focusing on Act.

Post Change Evaluation is often called the effectiveness review, and is a critical part of change in the pharmaceutical quality system, and frankly is important no matter the industry.

An effectiveness review is the success criteria of the change viewed over enough data points based on a methodology informed by the nature of the change and risk.

The success criteria should be achieved. If not, reasons why they have not been achieved should be assessed along with the mitigation steps to address the reasons why, including reverting to the previous operating state where appropriate. This may require the proposal of a subsequent change or amendment of the implementation plan to ensure success. Here we see the loop aspects of the PDSA lifecycle.

All changes should have a way back into knowledge management. The knowledge gathered from implementation of the change should be shared with the development function and other locations, as appropriate, to ensure that learning can be applied in products under development or to similar products manufactured at the same or other locations.

When choosing success criteria always strive for leading indicators that tell you how the change is working. Deviations are an awful way to judge the effectiveness of the change. Instead look for walkthroughs, checklists, audits, data gathering. Direct observation and real-time gathering and analysis of data of any sort is the best.

As mentioned above, ensure the change management/change control system is set up to deal with the inevitable change that does not work. Have a clear set of instructions on how to make that decision (returning to the success criteria), what steps to take to mitigate and what to do next. For example having guidance of when to create a deviation and on how to make a decision to rollback versus implement another change.

ICH charts a course

Last week the ICH published a reflection paper “Advancing Biopharmaceutical Quality Standards to Support Continual Improvement and Innovation in Manufacturing Technologies and Approaches.”

The ICH contines to move beyond the prescriptive guidances of Q1-7 and focus more on strengthening the conceptual framework of Q8-Q11 (see some of my thoughts here). There is a lot of talk about strengthening relationships and alignment between regulatory agencies, which is definitely needed. Q12 has had a bumpy road of it (EU saying they might not implement, US FDA issuing a guidance that’s not all that aligned). We see a firm commitment to continuing the QbD work with Q13 (continuous manufacturing) and Q14 (Analytical methods).

Interesting timing with the FDA recent announcement on generics.

International Plan of Mystery: ICH Guidelines for Generic Drugs

Back in October, FDA announced that it submitted a proposal to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) for the development of common global standards for generic drugs.
— Read on www.fdalawblog.net/2018/11/international-plan-of-mystery-ich-guidelines-for-generic-drugs/

Interesting blog post on FDA’s thoughts on the ICH creating some standards on generics.

Mylan Warning Letter

Mylan’s West Virginia plant received a Warning Letter this month and US FDA Commission Scott Gottlieb tweeted on it, and Mylan recently issued a press release.

I’ve made a few posts on their 483:

Mylan’s issues really need to be viewed as a lens of current regulatory body thinking and not as an issue of a company behind the times. In short, this could be you and if your company is not pouring through these and evaluating your own systems you should be.

The Warning Letter has a few trends we see in this sort of document:

Requiring an independent review. If your system is broke than the agency doesn’t trust you to say its okay. Get an independent consultant.
Lack of quality unit authority. One of the best things my site head of quality ever said (and if he is reading this, take this as a serious compliment) was to a group of high school interns when he said the quality unit is the only part of the Pharma manufacturing organization with duties required by law. That we have a legal duty to our companies and to the patients.
Go to the ICH guidance documents
This is happening at more than one site. Clean it up corporate wide.

The last one is worth further thought:

These repeated failures at multiple sites demonstrate that Mylan’s management oversight and control over the manufacture of drugs is inadequate.Your executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance. You should immediately and comprehensively assess your company’s global manufacturing operations to ensure that systems and processes, and ultimately, the products you manufacture, consistently conform to FDA requirements.

It is a critical part of your inspection program to be evaluating issues at each and every one of your sites for all your sites. The CAPA program needs to have the ability to assess CAPAs for similar root cause at all sites, that’s part of the preventive, and without it you are truly not addressing all the potential risks in your organization.

In past decades Mylan was a golden-child of cGMPs, and a lot of thought has gone into why the massive backslide. Cases like this, and Toyota, really reaffirm how a quality culture is something that must be constantly maintained and grown, and how easy it is to go backwards.