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FDA Protects Us From Terror of Unpasteurized Milk

August 8, 2011 By 5 Comments

Patrick Stone, President, TradeStone QA

I don’t know about you, but I sleep easier now knowing that our FDA has declared war on unpasteurized milk in America! It is not enough the US Government is fighting the war on terror (oxymoron) in dozens of countries, the war on drugs, the war on cybercrime, and now the war on unpasteurized milk. Yes, our tax dollars are hard at work, ladies and gentlemen.

For those just joining us, the results so far of these wars is economic collapse. Small business is the only hope for America now otherwise we might as well sign our souls to whomever owns our debt.

I am not sure that unarmed Amish & Quakers or any milk guild selling unpasteurized milk & cheese should be “taken down” with automatic weapons at the ready.  These are Americans trying to make a living.  FDA should educate food producers or show proof positive that adverse events/deaths have occurred from their dairy farm’s product — then go in without the guns blazing. Check the Constitution: innocent until proven guilty still applies.

Raw MilkAs a former inspector, I understand and did my duty when individuals knowingly caused harm or by acute negligence caused harm to another human.  But I feel ashamed to be associated with the FDA with this brand of overkill.

The burden of proof is on the government to show willful harm to the public.  I have not seen the “bodies stacking” up from individuals drinking unpasteurized or blending raw eggs into a protein drink.  An estimated 9 million individuals choose to drink raw milk each year with low ill effect (estimate by CDC, May 2011).

The CDC is a branch of HHS and tied to FDA; why are they on opposite sides of the table on this issue?  This is waste and politics at work with numerous health related issues causing death and disease waiting for FDA’s attention.  What is the real problem (Milk lobby)?

I do not condone “risky” behavior, however this is America and we can choose to live on the edge for freedom of choice.   How about making the consumer sign a waiver noting that they’ve been informed about the possible dangers and let them choose?

The possible dangers associated with consuming milk that is unpasteurized depend on the age of the consumer.  Vulnerable populations are susceptible to bacteria and viruses found in unpasteurized milk.  How do we know these individuals purchasing the “bad milk” are not heating or cooking this milk before consuming it.  The market sells many raw foods meant for cooking and there are many ways to get food regulation compliance.

Work with the market FDA, it’s your duty.

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

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Filed Under: FDA Regulated, Food, Patrick Stone, Regulatory Tagged With: , ,

Here’s Your Chance to Weigh in on FDA Compliance Focus

July 27, 2011 By Leave a Comment

Patrick Stone, President, TradeStone QA

The FDA is evaluating every regulated program in order to enhance compliance strategy. The drug program is on deck for the enhanced program evaluations and the agency will open the comment period for the next sixty days.

The enhancement in drug regulations will mean new drugs in the pipeline will take longer to get to market and the products on the market will endure post market safety studies for continuing evaluation of safety and effectiveness.

I would recommend drug companies make it clear in their comments that these FDA changes will make life tougher for small businesses and elongate the timetable they work with in getting new products to market.

I think that the already rising cost of health care will skyrocket to new highs when the enhanced drug regulations are implemented. Some of the proposed changes appear necessary but only time will tell what regulations are actually enacted.

That’s why it’s important for industry to weigh in with comments.

Combination therapies will have to include much more safety data or risk rejection from CDER. Animal studies (GLP) will be increased for toxicity and risk benefit.

I have observed that many good laboratory firms are conglomerating and outsourcing to far east partners. But the price of doing business out of country will not be cheaper in the long run. Shipping costs and intellectual loss will have to be factored into the great globalization effort.

Quality by design (QbD) is a pilot project now but its reference in the federal registry heralds the inevitable federal mandate. The actual report for new enhanced drug regulation may be found here.

Big pharma may be able to navigate the new ocean of regulation but what happens to the start-up biotech companies? Your voice counts for the next 60 days and then the new regulation will follow accordingly.

Make sure to follow Patrick on Twitter.

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Filed Under: FDA Regulated, Patrick Stone, Pharma/Biotech, Regulatory

At FDA, Looks Like ‘Transparency’ is Word of the Year

June 22, 2011 By Leave a Comment

Patrick Stone, President, TradeStone QA

Regulated health care industry professionals routinely request more guidance and transparency from regulators. New mandates for FDA have pushed modernization in an effort to promote transparency in government.

The FDA’s responses to this modernization request are the following FDA’s Transparency Initiatives:

Industry has also routinely requested to access compiled compliance actions and 483 lists of observations. The FDA has released the transparency websites in a effort to provide easy access to regulated industry trends and lists observations by program area.

FDA has also issued a summary of the most common inspectional observations of objectionable conditions or practices that are made during inspections. The implementation of a search based data portal that includes the names and addresses of inspected facilities, the date(s) of inspection, type of FDA-regulated products involved, and final inspectional classification.

The slow release of updated industry guidance for drugs, devices, and biologics should be the next focus area. Without enhanced guidance industry will continue to struggle with enhanced FDA inspections.

Possible budget cuts and user-fee money shortfalls may stifle many modernization initiatives including the transparency database up-keep. The transparency initiatives are beneficial for two reasons.

The system allows industry to understand that all the bad news is a quick click away as opposed to the slow freedom of information (FOI) request system and search enabled access. Regulated industry will now have quick access to view trend access for FDA focus areas to ensure the same mistakes are not continuously repeated globally.

This is a step in the right direction unless your business model depends on tracking and trending FDA regulated industry compliance actions for paying customers.

I hope the health care industry understands the vital resource now provided in an easy access form. The hardest part will be navigating the FDA website to find every possible resource available and pertinent to your industry program area.

Make sure to follow Patrick on Twitter.

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Filed Under: FDA Regulated, Patrick Stone, Regulatory Tagged With: ,

Protect Your Firm as FDA Inspections Spike for CROs, Sponsors

May 24, 2011 By 2 Comments

Patrick Stone, President, TradeStone QA

During the last two years of my time with FDA I noticed the amount of Sponsor and CRO inspections triple in number (for CDER, CDRH, & CBER).  CRO’s with less than adequately trained clinic staff and facilities to conduct human clinical trials are receiving warning letters and other FDA regulatory penalties.  The FDA has not conducted enhanced Sponsor or CRO Inspections in many years.  I have observed study sites get warning letters because monitors did not catch informed consent violations early in the trial or for other regulatory and subject record keeping violations.  Catching serious problems early in the trial can prevent adverse events, save time and assets in the long run.

Clinical Investigators and Sponsors  do not want to throw study data out due to preventable errors and inconsistent data.  Monitors for CRO’s and Sponsors should be proficient at the Quality Assurance (QA) they provide and be given adequate time at the study site to ensure regulatory and protocol compliance.

In my time at the FDA, even up to the end of my tenure this past March, I have observed CRO’s collecting original source site documentation from the clinic site at study close-out. I wonder how CRO’s seem to keep missing the basic reason FDA investigator’s conduct data-validation audits.  FDA wants to validate that source documentation match the case report form (CRF) and the sponsor provided data-listing with efficacy end points & adverse event lists.  CRO’s can easily scan the original documents into their system, but physically removing the source documents has conditions.

If a CRO truly wants the original documents for whatever reason, the CRO may certify each copy as a true duplicate of the original (21 CFR describes this process).  In many cases the Clinical Investigator relocates or there is no available space and money to store the records so the sponsor may step in to take over.  There’s not going to be any problem as  long as the FDA can follow the paper trail and review original documents as needed.   Copies may and have been found to be falsified so Investigators will not review paper copies of paper source records.  Electronic printout (output) is a different way to operate now and is acceptable for review.  Sponsors & CRO’s are using more electronic case report forms CRF’s & electronic records in general.  FDA is now requiring field Investigators to review computer systems for 21 CFR part 11 compliance & legacy system maintenance.

Do a search for your competitors’ recent FDA inspections and you will see the trend I am describing.  Build quality into your system from the ground up and you will get quality product results.  Trying to retroactively validate electronic systems and equipment or implement late stage corrections will leave you vulnerable to 483 observations.

You can follow Patrick on Twitter.

 

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Filed Under: FDA Regulated, Medical Devices, Patrick Stone, Pharma/Biotech, Regulatory Tagged With: , , , , ,

Institutional Review Boards Contend with FDA, OHRP

May 9, 2011 By Leave a Comment

Patrick Stone, President, TradeStone QA

I have noticed some concern from many IRBs about the GAO & OHRP difference of opinion regarding some aspects of human subject testing. If accreditation is ever fully pulled from an IRB, the reasons will be stated by FDA or OHRP. Through my review of many types of IRBs large and small (central & institutional) I have noted a few trends.

Central IRBs have two fundamental issues to deal with: quality assurance (QA) at the study site, and having a local representative of the community where studies are being conducted present at IRB meetings.

FDA & OHRP are now expecting IRBs to conduct QA audits as is done with most institutional IRBs. If the central IRBs can do a bit more with the funds they receive for service, they will survive this transition. The IRB’s basic functions are to insure patient safety & rights and assure clinical trials are following the CFR (all applicable sections).

In the end, the most basic function of an IRB is patient advocacy & record retention of patient safety discussions (for verification of review). Institutional IRBs in some cases do not scrutinize the in-house clinical trials adequately. In-house clinical trials do not get monitored as frequently due to lack of funds.

The institutional IRB’s should insure the name of the parent company/institution is tied to CFR compliant clinical trials, or the brand may be effected.

But I have a question for IRBs using electronic records: are you ready for the FDA investigator to challenge your 21 CFR Part 11 electronic record compliance? I have observed many large IRB’s staying in the paper records format. Due to cost & physical space issues, electronic is now the obvious way to go.

IRBs are getting more ICH audits and vendor qualifications which help IRBs stay in compliance with ICH guidance and the FDA regulations. FDA needs IRBs in good standing to review the many studies FDA field Investigators will not be able to Inspect. IRB’s play a major part in regulating clinical trials.

When I was with the FDA I always tried to encourage the IRB’s after a 483 was issued to do more for the patients and to effect real change in the amount of studies audited for QA. The FDA cannot get to every study or even thirty percent of the on-going clinical trials combined (biologics, drugs, & devices).

You, IRBs, do the heavy lifting for domestic clinical trial regulatory compliance. Thanks for the hard work.

You can follow Patrick on Twitter here.

 

 

 

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Filed Under: FDA Regulated, Patrick Stone, Regulatory, Warning Letters/Recalls Tagged With: , , , , ,

FDA’s Electronic Record Review Enforcement Policies Present Challenges

April 26, 2011 By 2 Comments

Patrick Stone, President, TradeStone QA

In 1999 the FDA released guidance for industry on the electronic records requirements for human clinical trials involving drugs, devices & biological entities (including the manufacturing of the approved products previously listed). In 2002 the FDA started training the field investigators how to review electronic records during routine inspections of human bioresearch and manufacturing for drugs, devices & biological entities. The catch was FDA investigators were not able to actually cite violations for 21 CFR Part 11 (code of Federal regulations) until approximately 2006.

The FDA instructed field investigators to only write up 21 CFR Part 11 violations if there were other non-Part 11 violations as well. One of the reasons it took so long to enforce the 21 CFR Part 11 violations was that fact that TurboEIR (FDAs report writing template system) did not have 21 CFR Part 11 483 cites. TurboEIR 483 citations became standardized because of the inconsistencies of 483s issued throughout the nation.

Fast forward to 2009 and the FDA starts to ramp up electronic record review for every firm that uses electronic records.

As an FDA investigator I have conducted many electronic record reviews and discussed many 483 cited observations with the Center for Drug Evaluation & Research and the Center for Devices and Radiological Health.

The most recent inspection I conducted for electronic records was a molecular diagnostic laboratory conducting testing for human clinical trials. This was a very special case in which I observed the clinical trial data did not match the data-listing provided by the sponsor. Long story short, the firm was using a data-stick to transfer original data-output and transferring it to an Excel data-set. Microsoft Excel® is not 21 CFR Part 11 compliant and the Excel® program cut off too many digits after the decimal place. The solution was an easy fix in that I suggested the molecular lab simply print out the original data and use that instead of the data-stick transferred data.

The Center put a short hold on the project until the reems of paper could be submitted in proper fashion.

The moral of the story is that as a sponsor or health care manufacturer you have to ensure that any projects slated for all electronic record submissions must be qualified and verified to comply with the electronic record regulation.

I will also give you one more example of a scenario where a project was held up by the agency for electronic record issues. I was inspecting a human clinical drug trial and I observed that source data did not match the sponsor provided data-listing because when the study was closed out and the data-lock was put in place it changed the audit trials and greyed out many data-points.

When choosing an electronic records vendor make sure that the data is never obscured or unreadable when the clinical trial is completed and data-lock is in place. You have to go from cradle to grave with your data and validate every step.

The FDA has made numerous electronic records exemptions for the Department of Defense and other U.S. Government agencies under the following exemption law (device products). A Compilation of Exemptions for Electronic Products Found in 21 CFR Chapter I, Sub-Chapter J — Radiological Health Parts 1000 – 1050.

However, the FDA does not currently abide by the electronic records regulation it enforces, for another case of do what I say, not what I do.

You can follow Patrick on Twitter: http://twitter.com/BIMOQA

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Filed Under: FDA Regulated, Medical Devices, Patrick Stone, Pharma/Biotech, Regulatory, Warning Letters/Recalls Tagged With: , , , , , , ,

What to Expect When the FDA Comes Calling

April 20, 2011 By 1 Comment

Patrick Stone, President, TradeStone QA

Enduring data validation audits and for-cause audits for human clinical trials involving biologicals, devices, or new chemical drugs may at first remind some of going to the dentist to get your wisdom teeth pulled.

But, the FDA has just as much at stake as your company does in the products marketed in the U.S., because if there is a problem or unsafe conditions FDA gets blamed for not doing enough.  That’s top of mind for most inspectors and important for regulated entities to remember.

With that in mind, let’s examine industry trends for these types of inspections.

Lets start by what Consumer Safety Officers (CSOs) look at first.  The regulatory binder is a road map of what happened during the clinical trial.  The IRB approvals, FDA approval documentation, and protocol versions are reviewed and recorded for the report.  The monitor reports and frequency of visits directly corresponds to the amount of observations FDA CSOs finds. So far, so good.

The areas most scrutinized for review are the protocol deviations & violations and adverse event reporting.  If a serious adverse event was not reported or not reported per protocol, you’d better expect a 483.  Failure to follow the IRB approved protocol version is the most cited 483 observation.

How does this keep happening over and over again? Easy: research clinic turn-over, lack of training on updated protocol or study procedures and the lack of monitoring.  The FDA is now requiring 100% consent form review of all subjects.  Failure to obtain informed consent with IRB approved document is the second most cited 483 item.

The third and most documented for clinical research 483 items is lack of complete or inaccurate source documentation.  The FDA is now requesting CSOs to audit the firm electronic systems and record any deficiencies on a 483.  The electronic records evolution started in 1999 and the FDA is now catching up and training CSOs to find your Part 11 computer system shortfalls and deficiencies.  Here, the FDA is turning to the ICH model as a bridge to the European Medicines Agency counterpart inspectorate.

The EMA model requires third party QA for every research trial which has proven to cut down on regulatory deficiencies.  In my opinion having that third set of QA eyes is all the difference between no action indicated (NAI) &  voluntary action indicated (VAI) from official action indicated (OAI) and a project hold.

Editor’s note: This is the the first in a series from our new blogger, Patrick Stone, M.S.  Patrick left the FDA in March 2011 after 12 years as a Biosresearch monitor at the agency’s Austin, TX office. He’s now President of TradeStone QA. While with the FDA, Patrick conducted domestic and international inspections of clinical investigators for pre-approval of pharmaceutical drugs, pharmaceutical drug manufacturing plants and domestic Institutional Review Board investigations.

As Stone recently told us, “I have worked closely with all departments (except foods CFSAN) CDER CBER CDRH and CVM. My work has gone through all of those department heads, too. I have 13 warning letters, one NDA revocation, and countless 483’s. I completed on average of 24 BIMO (clinical trial) audits every year since 2001 when I started conducting audits solo. It is my hope to bring some of that experience to readers of this blog.”

You can follow Patrick on Twitter: http://twitter.com/BIMOQA

 

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Filed Under: FDA Regulated, Patrick Stone, Pharma/Biotech, Warning Letters/Recalls Tagged With: , , ,
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