Compliance Zen

Six New FDA Enforcement Policies

This month saw the first glimmers of FDA's new "get tough" policy with the firms it regulates.  FDA Commissioner Dr. Margaret Hamburg laid out six policies that will go into effect over the next few months:

1. Firms are expected to respond to 483 observations within 15 days

This dovetails with the requirement for inspectors to forward their recommendations from the field as to whether or not a firm should get a warning letter or other enforcement action.

Unfortunately for executives who'd rather outsource a response to consulting companies that specialize in helping firms respond to 483s to avoid warning letters (a claim, I'd add, that few consultants back up with a money-back guarantee), 15 days is not a lot of time.  In that short span, you'd have to find the consultant; evaluate and qualify the consulting firm; craft non-disclosure contracts; write, revise, and sign the statement of work ... oh, AND also actually respond to the 483s.

If my experiences hold true of being called in to help clients AFTER the mess created by the "we'll save you with our awesome response" consulting firm back when the response time was 30-90 days, I'm thinking it's going to get a lot worse for drug, device, and biologics companies.  After almost a century of FDA, if you still don't realize you can't spend your way out of non-compliance as if dealing with FDA was a one-time project, maybe this industry isn't for you.

2. Swift and aggressive enforcement action by the FDA

The old days of multiple warning letters may be gone ... at least for the next few years.  FDA leadership is under fire by Congress and the GAO to actual demonstrate its ability to make manufacturers "do the right thing."  There's no point in having laws and regulations on the books if the agency is going to treat them as guidelines.

There's little doubt that one of the precursors for this announcement was the whole peanut debacle, plus the steady increase in consent decrees and corporate integrity agreements.

Again, based on my experiences, FDA says one thing but so often company executives hear something else.  Sometimes this is an excuse not to do something.

But sometimes, what is heard is impossibly  conservative, as in "The FDA says we have to secure our supply chain" being translated into "We need to audit and control every single company in our entire supply chain, from our actual supplier all the way down to the mine in the ground where they originally got the raw minerals that went into their supply chain that eventually found their way into our product."  Yes, really - that's a comment from a medical device executive at the recent FDA Supplier Quality Management conference in D.C.  Frankly, if we want to know where our high cost of healthcare starts, I'd suggest we clearly spell out that drug and device makers are not responsible for the quality of mineral mining operations and ore smelting....

There is a balance.  If you don't understand that balance, or how to derive it, get help before the agency does it for you.  The latter is called a consent decree and comes with millions of dollars of financial penalties and lots and lots of bad publicity.

3. Faster warning letter issuance

Thankfully, FDA will stop having its legal department review every formal enforcement action for wordsmithing, and just confine the legal review to actual legal issues.  This is something that a LOT of companies could copy.  I know I spent years working with a firm where every single SOP and Work Instruction had to be reviewed by the lawyers.  You'd send in a simple 3-page SOP and get back a 30-page SOP full of language like "...including, but not limited to..." and "...as deemed appropriate at the time of the decision with information immediately on hand or otherwise apparent..." and so on....

Turning things into legalese doesn't do much to increase people actually complying with them.

4. Timely inspection follow-up

Basically, instead of getting inspected and finding problems, issuing a warning letter, and then showing up 3-4 years later to see how you're getting on, the FDA will now issue a warning letter and show up sometime in the next 6 months to 2 years (depending on risk, criticality of issues, etc.).  People outside the industry think that's how it's always been.

Assuming that FDA cannot keep this type of timeline, look for the agency to be able to produce metrics showing Congress that "Hey, if you want this type of swift enforcement, it don't come cheap" and pushing for more funding.  What will be interesting to see is how Congress responds.  Earlier this year, I suggested levying civil monetary penalties to reimburse the agency for having to do re-inspections, issue warning letters, etc. - something that most consent decrees already have.  It's a model based on the "do not call" registry as well.  This past summer, members of Congress have started floating a similar idea.

For compliance executives who want to demonstrate bottom line value to their company, there is no easier way than to make a list of previous non-compliance actions that cost XYZ amount of money ... and then put in place controls to prevent those actions.

5. Warning letter closeout process

This has been a long time coming and well needed.  Today, FDA just removes the original warning letter from its website, rendering researching previous FDA enforcement actions a spotty, unreliable means of figuring out how to prioritize your compliance.

As I discuss in my FDA enforcement seminar, Bulletproof Yourself against FDA Enforcement, your job is to provide as much information in both record proof and summary form so that you make it easy for FDA to issue you a close out letter.  Remember, with shareholders and investors increasingly seeing quality systems and regulatory compliance failures "material information" that you need to disclose publicly, getting a "close out letter" is critical to avoiding investor lawsuits.

6. Increasing collaboration with other regulatory agencies

This is NOT just collaboration with international harmonization partners like members of the ICH or GHTF or Health Canada or the EMEA.  This also includes taking a cue from other US agency inspectors like those from OSHA or HHS (ala HIPAA) or SEC, or from state inspectors.  If those inspectors turn up issues, you should be expecting a phone call or knock on the door from the FDA shortly thereafter.

FDA harmonization is one of many issues I offer a lot of insight and advice on in my monthly newsletter, SmarterCompliance.

For instance, the FDA is working to knock down many of its barriers to cross-functional and cross-agency communications and coordination.  Kim Trautman of CDRH told executives from drug, device and biologic firms to stop seeing the GMPs and QSRs as distinct regulations only applicable to one type of firm or another.  And this is on top of last year's announcement that FDA would enforce ICH guidelines (followed promptly by the first warning letters citing ICH rules).  There should be little doubt that GHTF guideline enforcement is not far behind especially since FDA has been instrumental in crafting those rules as well.  FDA inspectors are being trained to look for your compliance with all of these.

To learn more ...

If you'd like to learn more about how to prepare yourself for stricter FDA enforcement in 2010, consider signing up for my September 29th webinar - Bulletproof Yourself against FDA Enforcement.  You can also download the detailed agenda here:  http://www.ceruleanllc.com/Webinar/default.htm

Are you ready?

August Newsletter Available

The August issue of my SmarterCompliance newsletter is now available.  Topics include:

• 17 lessons you can learn from the KV Pharmaceuticals consent decree with the FDA
• Steps to qualify virtual suppliers
• Four components of an FDA-approved CAPA process
• Making meetings matter every time
• Tips on avoiding a warning letter under the tough new FDA response rules
• and more....

Subscriber downloads include:

• Extended article on lessons from the KV Pharma consent decree
• A copy of the KV Pharma consent decree
• The original FDA Form 483 that sparked the KV consent decree
• EMEA guidance on biosimilar clinical and nonclinical development
• ICH guideline on biomarker submission requirements
• Six recommendations for the new FDA draft guidance

And I'm holding a special encore, updated version of my Bulletproof Yourself against FDA Enforcement webinar on September 29.  If you missed the first one earlier this year, don't miss this one with my updated advice on avoiding trouble in 2010.

You can get my monthly newsletter here:   http://www.ceruleanllc.com/Newsletter/Subscribe.htm

And if you're not sure if you want to subscribe, I do offer free 6-month trial subscriptions with my executive quick-start pack.  Alternatively, if you sign up for my mailing list at Cerulean, I'll be happy to send one or two issues free so you can decide if you want the trial or want to jump right in and start getting smarter about FDA compliance.

Details on the executive quick-start kit are here:  http://www.ceruleanllc.com/Toolkit/QuickStartKit.htm

Join my Cerulean mailing list here:  http://www.ceruleanllc.com/ContactReq.aspx

Featured Reading: Made to Stick

 

Would compliance seem such a chore to so many if quality manuals, security policies, records management procedures and audit reports were straightforward with simple, clear actionable takeaways?

That question hovers in the background the more you read through one of the best business books written in the past five to ten years, Made to Stick .

Drawing upon urban myths, corporate mantras and advertising slogans, Stanford University professor, Chip Heath, and former Harvard Business School researcher, Dan Heath, lay out what makes an attractive idea last and what makes a good idea fade.

Of particular help are the “clinics” in each chapter.  These pick a real-world concept that most readers will be familiar with (anti-smoking campaigns, for instance), and show how, using the techniques they’ve outlined, different groups have been able to either make the message memorable or forgettable.

Made to Stick is a necessity for any business leader, but its underappreciated value is for the compliance executive.

After all, assuming the content is the same, which sounds more enticing:  “Our  Quality by Design Strategic Initiative” OR “How We’ll Go from Lab to Market in 7 Years”?

Upcoming Compliance Events

This week I'll be

• conducting a teleconference for FOI Services on how to improve FDA-required training to get better results;
• serving as the chairperson for the FDA Supplier Quality Management Conference in Arlington, Virginia; and
• providing a one-hour session at the conference on how to set up a cost-effective, lean supplier quality management oversight program.

You can find out more about the FDA training teleconference on August 18th at the FOI website:  http://www.foiservices.com/.  Attendees will also get my "world famous" five-slide overview of FDA's quality system regulations (21 CFR 820) for device and diagnostics firms.  My colleague Nancy Singer, president of Compliance Alliance, will be discussing all the how-to's when it comes to ensure you have all the tools and proper learning environment in place.  FOI Services' Marlene Bobka will review a recent FDA 483 observation citing a firm for significant training-related issues.  And I'll lay out how to get more than just 13% of what you say to be retained by attendees.

The FDA Supplier Quality Management Conference is being hosted by FDAnews August 19-21, and features several speakers from the FDA discussing current supplier quality management expectations and enforcement trends.  Industry executives will also be on hand to share their successes and failures and lessons learned.  The conference is being broken out into 2 tracks:  one for devices and diagnostic firms; one for drug and biologic firms.

I'll be offering my lean supplier quality management talk in the device and diagnostic track.  If you're a biologic or drug firm and would like to take a look at the slides, give me a shout and we can arrange something; if there is enough demand, I'll simply schedule an online webinar / teleconference to walk through the whole thing and answer questions.

Hope to see you at one of the events!

Featured Reading: The Speed of Trust

 

A 2005 Harris poll revealed that only one-third of employees believe that their managers act with honesty and integrity.  As author Stephen Covey points out in his latest book, this lack of trust is the context in which executives must lead.

My featured reading, Covey’s The Speed of Trust , is a study in how trust influences the bottom line of corporations.  Throughout, Covey develops thirteen leadership behaviors that establish and grow trust among team, colleagues and departments in a company.

Two of these behaviors are of particular relevance to compliance and quality systems:

Behavior #9:  Clarify Expectations

Rarely are expectations clear or shared; they must be discussed and negotiated in the open.  The wise leader will recognize that even once expectations have been clarified and agreed upon, he or she must repeatedly communicate them.

Behavior #11:  Listen to Understand

I’ve often heard that we spend half our time talking and the other half waiting to reply.  Covey points out that active listening skills—really trying to understand—are a hallmark of a good leader.

To build trust in your compliance leadership and plans, learn The Speed of Trust .

 

August 2009 Events and Publications

This monthly update contains brief summaries of my recent publications and events that may help you in your current activities. Further information is accessed by clicking on the link provided at the end of each summary.

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Publication:  How to Meet Compliance and Records Requirements of the US Food and Drug Administration
Regulatory Affairs Journal has published my overview of how to implement a required records retention program to meet US FDA requirements.
Click to read more…

 

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Advanced Copy of Outsourcing Oversight Presentation

 

I've made an advanced copy available of my September presentation on how to prove to the FDA your outsourcing oversight and supplier monitoring program works.  Covers:

• Regulatory requirements for outsourced provider management
• Basic components of an outsourcing oversight program
• Six steps to take to prove to FDA inspectors you are in charge
• Key benefits
• Case study on outsourcing disasters to avoid

 

Available free to SmarterCompliance newsletter full subscribers – simply login and download.

 

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Teleconference:  Making FDA-Required Training Captivating – A Train the Trainer Session
On August 18^th, FOI Services hosts Nancy Singer and myself on how to design effective training presentations, how to encourage attendees to change their behavior, and how to teach the GxP and QSR regulations in five slides or less.

Click to learn more …  

 

FDA Supplier Quality Management Congress
I'll be chairing the FDA Supplier Quality Management Congress this August 19-21 in Arlington, Virginia, plus delivering a workshop for device makers on cost-effective qualification of suppliers.
Click to learn more …

 

Joint PDA / FDA Regulatory Conference
Join me September 14-18 in Washington, D.C. for the PDA and FDA conference, Securing the Future of Medical Product Quality: A 2020 Vision.  I'll be conducting interviews for his forthcoming book on personalized medicine and the challenges facing regulatory affairs and quality systems executives over the next decade.
Click to learn more …

 

8^th Annual Contracting and Outsourcing Conference
Back by popular demand, I'll again be speaking at Contract Pharma’s Annual Contracting and Outsourcing Conference in New Brunswick, New Jersey, September 24-24^th.  My talk will focus on supplier oversight and monitoring programs elements necessary to prove FDA compliance.
Click to learn more and get an advanced copy of the slides …

 

August Issue of SmarterCompliance^™ Newsletter
This month’s issue of my FDA intelligence and quality systems advisory newsletter is set to be published the last week of August.  Topics include:  an analysis of and recommendations from a recent FDA consent agreement; tips for selecting, qualifying, and monitoring virtual suppliers; and more.
Click to learn more and subscribe today...

 

 

Recent Regulatory Documents of Interest:

 

·         EMEA-FDA Joint GCP Inspections and GCP Harmonization Initiative.

http://www.emea.europa.eu/pdfs/general/direct/internationalcoop/EMEA_FDA_GCP_Initiative_2009.pdf

 

·         Genomic Biomarkers Related to Drug Response. ICH E16 Step 2 and FDA draft Guidance  http://www.ich.org/LOB/media/MEDIA5518.pdf

 

·         Assessing the Reliability of Computer Processed Data. GAO Report  http://www.gao.gov/new.items/d09680g.pdf

 

For FDA forecasts and expert advice on regulatory compliance, quality systems, and trends that affect you and your organization, subscribe to my SmarterCompliance^™ newsletter online.

Lean FDA Compliance Self-Assessment Quiz

Every year, I try to give subscribers to my newsletter various checklists and other free downloads related to effective FDA quality systems and regulatory compliance.  Last year, one of the checklists I provided was a self-assessment so subscribers could see how their quality systems, regulatory affairs, and compliance programs stacked up to best practices around effectiveness, proactivity, and cost-efficiency.

Questions included:

• Are your SOPs and policies written for readability and usability (e.g., score between 6-10 on the Flesch-Kincade Grade Level)?

• Is a cross-functional team used to walk through any drafted SOP or policy to identify gaps, bottlenecks, duplications, or inefficiencies?

• Do you hold a quality systems and regulatory affairs program management review at least once a year?

• Does your over-arching quality policy include quantitative targets against which to measure results?

• Do your SOPs and policies reference ICH and/or GHTF guidelines in addition to FDA regulations?

If you'd like to download your own copy of a current self-assessment checklist, including a ratings scale, you can do so here:  Download 38-Point Lean Compliance Self-Assessment

This five-page self-assessment has 38 "yes/no" questions you can quickly review and answer.

Best to do so before the inspector ... or your annual compliance review.

Quality by Design Frequently Asked Questions

Whenever I speak at companies on how to adopt and implement Quality by Design – whether in preclinical, clinical, pilot manufacturing, postmarket, and so on – four questions consistently come up:

 

Is Quality by Design like the old "process validation"?  We do all this work and get nothing in return?

In 2008, when I, along with the FDA’s Helen Winkle and Moheb Nasr, spoke at the PharmaQbD seminar, Helen pointed out that Quality by Design is the first real change—from top to bottom—of how we develop, test and manufacture medicines in over 25 years.

Based on my experiences outside the FDA regulated industry (see my 2006  article, “Elucidation:  Lessons from the Auto Industry”), I anticipate the entire product lifecycle approach will be very different within the next 10 years in the biopharma sector.  No longer, will we just “follow the science” - the marketplace simply cannot afford it.

Quality by Design is ultimately about figuring out how to balance safety, efficacy and quality with our bottom-line realities.

 

Does the FDA require us to comply with Quality by Design?

FDA officials (Kim Trautman, Janet Woodcock, Moheb Nasr, and others) have repeatedly announced at various industry conferences over the past 2 years the need to comply with Quality by Design and other ICH guidance. I give attendees at my workshops a special FDA industry report I authored that contains specific recommendations from FDA officials plus my own analyses on how to smoothly translate these ICH expectations into your environment (you can get your own copy of “FDA Quality by Design Expectations and Modern Quality Systems” on the Cerulean website).

You should also review warning letter 320-08-01 (April 21, 2008).  On page two is a citation for lack of ICH compliance, “The ICH Q7A Guidance (Laboratory Controls, General Controls) states that appropriate specifications should be established for APIs, including for control of impurities.  Your firm failed to establish….”

The agency is not participating in either ICH or GHTF regulatory harmonization efforts out of the kindness of their hearts.  Expect to build quality into your medicines by design or expect to be out of business in the next 20 years.

 

In July 2008, the FDA published a call for participants in a Quality by Design pilot for new biotech products—I thought Quality by Design was only for pharmaceuticals?

The pilot submission program (Docket No. FDA-2008-N-0355) is an example of the growing convergence of FDA regulations that govern pharmaceutical, biotechnology and medical device firms. Officials have repeatedly stressed, since the publication in 2004 of the cGMP initiative for the 21st century, their desire to streamline all the regulations governing these industries into one set of “medicinal product” rules.

Combined with the FDA’s expectation (see my “FDA Enforcement Report 2008-2009” compliance report) for companies to adhere to the ICH, it would be fair to assume that the eventual single set of regulations will look very similar to the ICH and GHTF guidelines. Both the EU and Canada are on the same track and the FDA, EU and Canada just signed a joint inspection agreement.

 

Can Quality by Design help us  draw the line between R&D work and more formal preclinical design and development activities?

Answers on this question range from as late in the development and design process as possible (putting it very close to Phase I clinicals) to as early as permissible in R&D to avoid having to redo any tests for inclusion in an eventual submission.

Consider drawing the line using the patent application as the demarcation.  Formal preclinical design and development activities should start when you begin the patent application process for a product you intend to commercially distribute/produce or otherwise license. Consider drafting company guidelines on this with your legal counsel and an outside, independent expert to advise you.

For further details on preclinical development and Quality by Design, see my article, “Using Quality by Design to Define Your Preclinical Package” in the Autumn 2007 European Biopharmaceutical Review.

 

How can we stay current with FDA Quality by Design expectations and industry best practices?

In addition to regularly checking in on the FDA and ICH websites, you can also monitor a growing number of websites that publish some material (most of which is ad-supported or sponsored by multiple vendors that sell PAT technologies and consulting services).

For a vendor-neutral, more independent approach, consider subscribing to my monthly quality systems and FDA compliance newsletter, SmarterCompliance™.  I offer a free trial subscription with which you may want to test the waters.

 

Got any other questions on Quality by Design?  You may want to download my free PDF executive guide to the FDA’s Quality by Design.

Featured Reading: Design for Six Sigma

 

If your organization is Six Sigma focused, the new product development methodology outlined in this book is a necessity.

If you are not Six Sigma focused but are seeking ideas on how to speed your development and lower costs, consider reviewing and adopting some of the tactics in Design for Six Sigma .

And if you are looking for help implementing the FDA’s Quality by Design initiative, this brief book should give you much food for thought.

Broken into nine chapters, the book outlines the overall strategy for implementing Six Sigma in a product design environment.  Along the way, the most relevant tools and statistical methods are highlighted.

Every chapter ends with a concise “manager’s checklist” of the most important concepts from the chapter (something that I’m trying to adopt for the book I’m currently working on).  Other reviews of this book have focused on how it is not an in-depth resource on applying Six Sigma to product development; I rather like it's tight, summary points.  If you're looking for the textbook on Six Sigma and new product development, this is not the book; if you're looking for a quick refresher you can skim and look for specific techniques, this is perfect.

While most of the book is applicable to firms under US FDA or other HHS regulation, the examples are almost entirely drawn from the consumer products industries.  The usual suspects from any write-up on Six Sigma are all present—Motorola, GE, and so on.

All round, the Design for Six Sigma is a good read for any executive, especially those in research, development and commercialization.