Michael Causey, Editor & Publisher, eDataIntegrityReport.com

One of my favorite all-time bands, The Kinks, have a fantastic tongue-in-cheek song called “Have a Cuppa Tea” that satirizes the British belief that a good hot cup of tea will solve all of the world’s problems.

• 820.198 Complaint files
• 820.90 Nonconforming Product
• 820.80 Acceptance Activities
• 820.200 Servicing
• 820.22 Audits
• 803 Medical Device Reporting (MDR)
• 806 Reports of Corrections and Recalls…

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Deciphering the FDA is a bit like trying to understand what the old USSR was up to in the days of the Cold War.  In those days, it was called Kremlinology, or the study of a complex, secretive organization.  We need a catchphrase for those of us today who try to figure out what the FDA means when it says something, or what it means when it says nothing, or what it means when it tells you what it means. You get the idea.

The FDA has been talking a lot of late about transparency. Its 2011 initiative is an agency attempt, it says, to open up about how it does business. FDA is accepting comments on it until February 28.  The jury is still out on whether this initiative will accomplish much.

Our latest piece of FDA evidence is CDRH’s 2012 Strategic Priorities.

CDRH devotes the Introduction of the document about looking ahead to patting itself on the back for its 2011 achievements, e.g. its report, “Understanding Barriers to Medical Device Quality,” that reviews the challenges that the FDA and industry face in supporting well‐integrated, best‐quality manufacturing practices and strategies that industry and the FDA can take to overcome these barriers.

CDRH also reminds us that “to complete this work [in 2011] our staff went above and beyond their already demanding workload. This is a remarkable achievement.”

Good to know.

In 2012, CDRH says it will continue to emphasize four priority areas:

1. Fully Implement a Total Product Life Cycle Approach
2. Enhance Communication and Transparency
3. Strengthen Its Workforce and Workplace
4. Proactively Facilitate Innovation to Address Unmet Public Health Needs

CDRH promises in 2012 to “improve” its premarket programs. By April 1, it pledges to begin its Triage of Pre-market Submissions Pilot to “increase submission review efficiency and better manage the pre-market review workload.”

And by the end of the year, CDRH pledges to publish a proposed rule to clarify the circumstances under which it could rely on clinical studies conducted in and for other countries. CDRH also says it will finalize all guidance documents it has issued as part of its overall plan to improve its premarket programs.

We’ll keep an eye on these and other promises throughout the year and report back as FDA hits or misses its own targets.

Patrick Stone, President, TradeStone QA

In the age of electronic documents and electronic signatures, the FDA is still defining and providing guidance for 21 CFR Part 11 concepts it began in 2003.  It seems we all really need to catch up.

Now that FDA provides small business webinars and blogs about “the most pressing public health issues of the day”, it is refreshing to note that FDA does not deem all electronic records as regulated; however with human clinical trials, most if not all records are reviewable (investigator discretion).

Basic concepts like hybrid records (paper based, e-records) and meta-data (audit trail data-points) should be well defined by now and not mysterious to industry.  Enforcement discretion still applies for most Part 11 electronic review by FDA investigators.

The new risk based approach will need to be well documented and defined before approval is granted by the respective review division.  In 2007, FDA provided the most up to date guidance and current thinking on computer systems used in human clinical trials.

Once you can establish and document these three risk based controls you are ready to begin your clinical trial. The risk based approach continues throughout all phases of your clinical trial.

Companies conducting clinical trials in the all-electronic environment with e-patient source, e-case report forms, and scanned regulatory records may find that costs go down. You have spent multi-millions in assets to implement validated e-systems so now you may use “alternative monitoring” methods for your monitoring controls.

Human clinical trials can be monitored from a desk if your monitoring plan is deemed acceptable to the review division. You do not necessarily have to pay travel expenses for multi-site monitoring anymore. Here is the game changing draft guidance for “Oversight of Clinical Investigations  A Risk-Based Approach to Monitoring” and I have also included the link for the 2012 Small Business webinar “Electronic Source Documentation in Clinical Trials” here.

There’s more to this subject and we’ll revisit it again.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

To salt or not to salt? That is the question. Well, it’s one of the questions.

It’s actually bigger than a battle over a popular condiment, according to some folks who oppose what they say is the FDA overplaying its regulatory hand.

We’re not going to settle this controversy here, but some experts suggest you may be able to sprinkle a little salt on your food without feeling guilty about increasing your risk of heart disease and high blood pressure.

However, some say the FDA has gotten too activist and one-sided in its approach to the condiment – and that it’s just another sign that the FDA in 2012 will be more strident with regulatory overreach that won’t help food consumers and will harm food manufacturers.

The FDA is generally following the lead of a 2010 report from the IOM that says salt contributes to serious health problems. The agency is working on a guidance now that would promote ways to reduce salt consumption by Americans in their diet.

“I think the FDA is adding unnecessary bureaucratic layers” that aren’t improving food safety and are in fact making it harder for food manufacturers to do business, says Julie Gunlock, a senior fellow at the Independent Women’s Forum, a non-partisan research and educational institution that seeks to combat what they say is the too-common presumption that women want and benefit from big government. In the case of salt, for example, Gunlock says the FDA is ignoring more recent studies that at least question the strong connection between salt and the health problems.

Gunlock has written extensively about what she calls “the damage” caused by intrusive FDA regulations. She focuses on the harm to food processors and manufacturers, and the role of parents in making dietary decisions on behalf of their children.

For Gunlock, it’s more than just a battle over salt. She sees this issue as just another example of the FDA taking authority away from state regulators and telling consumers what they can eat. “Unfortunately, I think we’ll see tougher FDA actions in 2012 against a food supply chain that is already safe and probably doesn’t need additional regulation like this.”

When trying to predict what will happen in 2012, it’s important to recall that the Food Safety Modernization Act, signed in January 2011, ushered in a new era of increased security measures, processes and controls for food safety officials; most orchestrated by the FDA, notes Don Hsieh, director of commercial and industrial marketing with ADT Security Services. He works to educate brands on how to build a proactive food defense program and how food officials can effectively comply with FDA regulations.

Simply put, the FSMA is the” most significant expansion of food safety requirements and FDA food safety authority in over 70 years, since the original Food Drug & Cosmetic Act in 1938,” Hsieh says.

And FDA is clear on its intent. “The historic FSMA is aimed at transforming our food safety efforts toward prevention and based on risk analysis” said LeeAnne Jackson, PhD, Health Science Policy Adviser, FDA.

Hsieh reminds us that recalls are bad for business, to put it mildly. One of the largest food recalls was the recall of peanut products produced by Peanut Corporation of America. What resulted from this mass distribution of contaminated product were 714 confirmed infections, nine deaths and $1 billion in losses to the United States peanut industry. The Peanut Corporation of America filed for Chapter 7 bankruptcy and its owner and CEO appeared before Congress under Congressional subpoena. Although the cause of the outbreak was one firm and did not involve major peanut butter brands, consumers reacted by avoiding the peanut butter category and sales plunged 25% after the recall announcement. “This points out the importance of not only protecting the food supply chain for your company’s products but being able to prove that your supply chain was not impacted by a specific incident,” he sums up.

But are food processors ready for 2012? Doesn’t sound like it. As Hsieh points out, for most food manufacturers, “documentation is typically done by a person with a clipboard checking off items on a paper check-off list. Given FDA’s mandate of providing documentation of compliance, these documents may not accurately reflect compliance and are difficult to access and compile.”

Looking ahead to 2012, that’s probably an understatement.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Business Intelligence (BI), the process of transforming the raw data companies collect from various operations and sources into usable and actionable information, is an often under-utilized and misunderstood tool in the strategic arsenal.

A new white paper from Information Builders by Kevin R. Quinn notes that companies are increasingly leveraging BI software to help them aggregate, manipulate, and display data to further inform their decision-making. Harnessed properly, this can improve the way companies do business if they utilize the proper business intelligence improvement cycle (BIIC).

But many companies fall short of their BI potential for several reasons, including:

• Users’ skills and desires are misinterpreted.
• An emphasis is put on the wrong stage of the cycle (plan, improve, measure, and analyze).
• No information self-sufficiency.
• No culture of established measurement.
• Disparate tactical BI solutions gain footholds.

Let’s look a little more in-depth at how these common pitfalls trip up companies.
SKILLS MISINTERPRETED: There are four categories of information workers. Nontechnical business users, who tend to make up 80 to 90 percent of the workforce, business analysts, power users, and IT developers. Quinn says that too many organizations focus all of their BI resources and tactics on the business analysts and power users, this prevents “the majority of users from using the tools and becoming part of the information culture.”

WRONG EMPHASIS: Quinn argues that companies often neglect the first stage, planning or gathering information, in their haste to get to the good stuff. As the old computer adage goes, “garbage in, garbage out.” Planning and collecting information may not be as fun as working with the data, but it’s the foundation for the success of any big BI project.

LACK OF SELF-SUFFICIENCY: A common pitfall when setting the BIIC in motion is that the IT department is relied on as the sole information-producers in the company, while of course they aren’t the only group that generates data. “This causes an imbalance that leads to a heavier burden on IT because as more and more information consumers need information, more and more requests are made of IT.” Making matters worse, IT personnel frequently don’t understand the underlying nature of the business questions that data users are looking to answer, so their responses are often incorrect or incomplete in practical terms.

NO MEASUREMENT CULTURE: We’ve emphasized this before. If there is not buy-in at the top, any initiative is most likely going to fail. No exception here, Quinn says. “If executives are the only people who are about measurement and the improvement of those measurements’ outcomes, the motivation to improve will not be established among the ranks of workers who have the capability to make the necessary changes.”

DISPARATE SOLUTIONS: Quinn writes that many organizations purchase BI tools without a clear strategic plan for using them to truly make changes within the organization. When reports are generated at the behest of a Big Cheese, for example, rather than being part of a bigger BI plan, key reports and key information is often locked in figurative silos without contributing to a smooth-flowing BIIC.

Quinn advocates a simple method of information access and distribution along with open communication within an organization to ensure that everyone understands the value of BI and why an intelligent BIIC is a critical component of success in today’s marketplace.

Editor’s Note: To read the full white paper, click here. Note: Registration is required.

Patrick Stone, President, TradeStone QA

Will 2012 be a Mayan prophecy year of doom and gloom at FDA or will they get the job done for US/global public safety? According to the FDA website, 2012 will be a year of global regulatory operation and enforcement with emphasis on medical devices, drugs, and food products. Will the 2012 budget from congress for FDA provide the necessary funds as supplemented by MDUFA and PDUFA to complete this global mission?

Third party audits may be a new driving force in the completion of this bold global mission as with the European Union ICH mandates. How will FDA review the third party audits and enforce them accordingly?

The growing pains of letting go of the steering wheel may take FDA some time to get used to. Trusting international “accredited” third party audits may take some time for FDA to digest, too. FDA is used to being in the driver seat for all aspects of firm review and enforcement especially for medical devices and drugs. There may be an uptick in regulatory action internationally and some more supply chain shortages in both medical devices & drugs due to expanded review process.

Domestically, FDA will try to inspect the few medical devices & drugs manufacturing firms left within our borders. The focus may be on dietary supplements and food firms in order to meet congressional mandates for the Food Safety Modernization Act (FSMA). I can only hope that FDA mandates better labeling for our food products with strict guidelines on labeling the percentage of that food product which is imported.

According to FDA,”Nearly two-thirds of the fruits and vegetables–and 80% of seafood–eaten domestically come from outside the U.S.”

As consumers we need to be able to make informed decisions about the food we eat and where it is harvested. Processed foods are not labeling the percentage of imported ingredients within their product. FDA should also focus on human clinical research domestically with an emphasis on training inspectors to complete this goal. We may have lost domestic manufacturing for medical devices & drugs — however human clinical trials have not decreased at the same rate.

Clinical trials must be conducted domestically in order for the test article to be marketed in the US. Logic should dictate that FDA review more of these medical devices & drug human clinical trials. Unfortunately political appointees with no FDA experience lead the mission here, so logic and science are not always a driving force. The field investigator can only do what they are told not what is logically necessary to complete the public safety mission.

Crystal balls aside, let’s hope 2012 is a better year for the FDA.

Read more about FDA’s 2012 inspectional and enforcement trends here.

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.

Kim Egan, Partner, DLA Piper LLP

Earlier this month and just in time for Thanksgiving, the Department of Agriculture’s Economic Research Service issued a report called How Much Time Do Americans Spend on Food?

The findings include some things we already knew, such as women spend more time grocery shopping than men do, and obese people watch more television than “normal” people do. Men raid the refrigerator at night more frequently than women do. People who live alone are more likely to eat alone. Etc.

The findings include other things we may not have known already but that seem fairly obvious, such as poor people spend less time eating and drinking than people with higher incomes, and people who eat in front of the television are fatter than people who eat while doing pretty much anything else.

The rest is pretty interesting:

• On average, adult Americans spend 67 minutes a day doing nothing but eating and drinking, and 23.5 minutes a day eating and drinking while doing something else (working, driving, watching TV). That’s about half an hour per meal, assuming three meals a day. I don’t think that’s enough.
• Eleven percent of the population spends at least 4.5 hours a day eating and drinking. That’s more like an hour and a half per meal. Much better. If I had my way, I’d spend an hour with breakfast, an hour with lunch, and at least 1.5 to 2.0 hours with dinner and dessert, interspersed with nice snacks. My family spent 3.2 hours on Thanksgiving dinner (excluding snacks and appetizers).
• Another 11 percent of us are what USDA calls “constant grazers.” These are people who spend 75 minutes a day doing nothing but eating and drinking, 2.2 hours eating while doing something else, and 8 hours a day (i.e., ALL DAY), doing nothing but drinking, which is defined to exclude water. That comes to more than 11 hours of eating and drinking every day — most of a normal person’s time awake. If these people didn’t need to sleep, they’d probably eat more.
• Four percent of us appear never to sit down to a proper meal at an old-fashioned dinner table. Instead, we spend all our eating and drinking time doing something else as well (mostly watching TV). I would have expected that figure to be higher.
• People in the Northeast and the West spent more time eating than anyone else. The study didn’t look at this but I suspect average BMIs are lower in those regions as well.
• Almost 70 percent of Americans do their primary eating and drinking at home. Only 0.2 percent of us do our “primary eating” on a “mode of transportation.”

What the study did not research is what percentage of meals eaten every day are home-made. That would be interesting to study. Just because one eats at home does not mean one eats well. Especially if one is a “constant grazer” and one spends 8 hours a day drinking something other than water.

Kim Egan is Partner in the firm DLA Piper LLP

You can also follow her here on Twitter: http://twitter.com/kkegan

Patrick Stone, President, TradeStone QA

The Obama Administration’s recent Executive Order Reducing Prescription Drug Shortages states that some health care providers may hoard drugs that are in short supply.

I am wondering how this is possible if the drugs are not even available to hoard? In this Executive Order it specifically states that root cause analysis and solutions may be out of FDA control. Only the US Congress may appropriate funds for HHS/FDA work force initiatives.

According to the Executive Order, pharmaceutical manufacturers are requested to report timely drug manufacturing discontinuances. But the order clearly misses some important points. The problem is that FDA already knows about drug discontinuance when they order a hold on product or issues a 483 for GMPs with a warning letter follow up.

Moving drug manufacturing out of our country further compounds this drug shortage. It may take years for a drug firm to re-start operations after a move from the US. The fact our US government gives incentives to big drug manufacturers to leave the US with huge tax breaks is also part of this problem.

Shipping drug manufacturing to India and China for cultural exchange or to bring up the standard of living is a slow process filled with FDA/GMP regulatory pitfalls. Expedited regulatory review must take place where the pharmaceuticals are manufactured, many of which are overseas.

I am not sure how this is possible when most of the FDA’s funds are already earmarked for FSMA food priorities and congressional mandates. I do applaud Sec. 4 mandating the FDA to communicate with the US Department of Justice (DOJ) on price gouging and hoarding to seek enforcement actions. I am still wondering how hoarding will be possible if the drugs in short supply are not available at all.

This short and sweet Order will hopefully prod the US Congress to address this problem with the full force of the US constitutional authority. Time is a luxury factor we do not have. As I stated before in a previous blog, the pharmaceutical industry and FDA must collaborate to mitigate further risk to national security.

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

The FDA has to speed up adoption of a “Benefit-Risk Framework” to improve decision-making in the regulatory process, said John Lechleiter, Ph.D., chairman, president and CEO of Eli Lilly and Company.

Speaking at recent industry conference, the CEO of the drug giant called for a regulatory process that focuses both on recognizing and appreciating benefits while identifying and minimizing risks. Such a balanced approach would help increase the flow of needed medicines to patients and reverse a trend of fewer new drugs getting approved, he said.

“The stakes are high,” Lechleiter said. “The only way to make inroads against [chronic and other] diseases is to sustain the pace of medical progress.”

The FDA appears to be a bit on the defensive here. It recently issued a report touting its record approving drugs it says demonstrates it isn’t stifling innovation at all thank you very much.

The backdrop to this battle is the upcoming reauthorization of the Prescription Drug User Fee Act (PDUFA) V. Originally enacted in 1992, PDUFA and its iterations set the foundation for how FDA will manage the drug review process for five years, beginning in October 2012.

Lilly’s Lechleiter stressed the importance of a non-partisan course for reauthorization. “As a basis for the drug review process, PDUFA is too important to get bogged down in partisan politics,” Lechleiter said. “As Congress considers reauthorization next year, we hope to see a ‘clean’ bill – one free of extraneous and controversial provisions that would politicize the bill and further complicate matters for all parties.”Lechleiter said the regulatory system must continue to evolve to meet 21st century needs.

Lechleiter offered five key characteristics of a “state of the art” regulatory approval system:

1. Timely – “There are far too many conditions for which therapy is inadequate or nonexistent. We need a system that is not only effective, but efficient as well.”
2. Predictable – “The system must be predictable in its judgments, its decisions, and the criteria on which those decisions were based – whether scientific, ethical, legal, etc.”
3. Consistent – “The system must be consistent across review divisions using standardization and repeatable processes – so that an innovator clearly understands the regulatory requirements and so that institutional learning can be harnessed to replace time-consuming one-off learning by review groups and division.”
4. Transparent – “The system needs to be transparent in its judgments and criteria so [stakeholders] understand the rationale for its decisions.”
5. Scientifically rigorous – “This requires scientific expertise within the agency – or access to the expertise – that understands, engages in, and influences the constantly evolving external scientific environment and ensures that standards are up-to-date.”

Lechleiter also discussed ways to strengthen a medicine’s benefit and lower its risk, including calling for greater emphasis on improved outcomes for individual patients, through the development of tailored therapeutics.

“From the point of view of patients and their doctors, a tailored therapy will provide a better benefit/risk trade-off, because they can have a higher degree of confidence that it will work effectively and with minimal harmful side-effects relative to the benefit obtained,” said Lechleiter. “From a value-for-money standpoint, tailored medicines should also reduce the heavy costs associated with non-responders. In other words, payers will get what they are paying for.”

Cry havoc and let slip the dogs of war. This one isn’t over by a long-shot.

Patrick Stone, President, TradeStone QA

Here’s an idea: More FDA inspections outside the US, at a lower cost.

How?

If FDA trained other countries health organizations to conduct FDA business with Memorandums of Understanding (MOU), less money could be used to travel with more inspections completed. This training could be accomplished online and by going out with FDA International Investigators. The EMA should have a MOU if their model is similar to FDA’s. The advent of all electronic review should alleviate the need for more international inspections.

I admit I may be over-simplifying the issues with training monies and bringing foreign inspectors to US training facilities. But I think the basic idea holds water.

Host nations can send their inspectors for knowledge sharing and training with justifiable beneifits to the host nations public health. FDA can also video link for training, as is done currently for new hire training.

Unfortunately, innovative options are scarce at the FDA Senior Executive Service level (SES) and the old way of doing business is ingrained into the government model. For the short term FDA will try to increase international inspections in all program areas with a focus on food work.

I’ve observed many international drug and device firms receiving warning letters and multiple item 483 forms. If this current warning letter trend continues, the blame may fall on lack of FDA regulatory guidance.

The core mission of FDA is to protect the US public from harmful health products. Sending FDA field Investigators to where the products are manufactured and undergo human clinical trials is one of the only ways to accomplish the core mission. Ensuring that field investigators are proficient for the task and seasoned investigators stay engaged will be the challenge.

The international firms with compliance issues should be reviewed by their country’s FDA equivalent for cross training on regulatory compliance.

On the job training is used here at home as a component of new hire training. FDA will have to think outside the box if Congressional Mandates for International travel are to be met.

Congress must also understand that it is not only the amount of funds that insure successful international travel, it is also about proficient field investigators as well.

I have faith that FDA field staff will answer the challenge because they always do.

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.