FDA Warning Letter to API Drug Manufacturer in China

The U.S. Food & Drug Administration has sent a Warning Letter to a manufacturer of active pharmaceutical ingredients (APIs) in China for violations of current good manufacturing practices (cGMPs).

The increased globalization of the pharmaceutical industry means that a finished pharmaceutical obtained by a consume at their local pharmacy can have components manufactured in a number of different countries and the finished dosage form manufactured in another country altogether. Problems with heparin and other drugs manufactured abroad have raised imported drug safety high on the list of FDA’s public health concerns.

Over 90% of active pharmaceutical ingredients (APIs) used in U.S. drug products are imported

The FDA Warning Letter, dated January 28, 2010, does not indicate if the inspection was initiated by one of the new FDA resident posts in China that have been opened to enhance food safety, drug safety, and the safety of medical devices.

On Tuesday, November 18, 2008 The U.S. Department of Health and Human Services issued a press release that stated:

“FDA has selected eight senior experienced FDA officials to work in its offices in China. The employees are inspectors and senior technical experts in foods, medicines and medical devices. The HHS/FDA office in Beijing will be located in the US Embassy. In Guangzhou, it will be located in the U.S. Consulate General, and in Shanghai it will be part of the U.S. consular mission there, but will be situated in the Shanghai Centre, a well-established business complex in the city where several other U.S. government agencies have staff.”

The FDA Warning Letter has serious concerns regarding the testing for the APIs stating:

“For example, your quality control unit failed to detect that IR spectra were being substituted by a laboratory employee and therefore, misrepresenting the actual results of the tested incoming material. Your response is inadequate in that it does not address the ability of your quality unit to control and detect the manipulation or alteration of laboratory documents.”

Here’s the Warning Letter:

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm200384.htm

These are serious charges and are a cause for concern by any consumer using drug products. Since 2008 FDA has also issued Warning Letters to a Japanese firm and another Chinese facility for drug safety and failure to follow cGMPs for active pharmaceutical ingredients. This indicates a continuing concern over the quality of APIs. Over 90% of APIs used in drugs in the United States are manufactured abroad. Opening resident posts in China, India, and other countries is part of the effort to ensure their safety.

GxP Perspective:

Regulating APIs is not an easy task. The FDA GMP regulations are for Finished Pharmaceuticals. You will note that most FDA Warning Letters cite FDA regulations found in Title 21 of the Code of Regulations (21 CFR). Warning Letters for APIs however, cite the Food, Drug, and Cosmetic Act and the U.S. Code (U.S.C.). In 2000, when I joined the FDA Foreign Inspection Cadre, FDA headquarters staff actively recruited new API inspectors from the foreign cadre because so few API inspections took place in the United States. When I went to API school we were taught to use the International Conference on Harmonization document Q7A as an inspection tool as a replacement for the 1991 “Bulk Pharmaceutical Chemicals” inspection guide. The API Compliance Program Guidance Manual for APIs was issued in 2006 and incorporates Q7A. This is a great step forward, just as the establishment of foreign resident posts improves FDA’s ability to monitor the production of APIs.

I conducted API inspections in Canada, France, Ireland, and the U.S. They are not an easy inspection and should be conducted by specialists. Fortunately I had the opportunity to work with a really great chemist, and that made my job a lot easier.

With the globalization of drug, device, and food manufacturing we want the best inspections possible. Ultimately that will mean increased cooperation and coordination with other regulatory agencies. That is one area that definitely needs improvement. It seems the current FDA leadership senses the need to improve international cooperation. They’ve got a big job in front of them.

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One year for the Blog

This blog started on 16 February 2009 as “Carl’s Blog on FDA Stuff.” At the time I said:

“This blog will attempt to discuss some of the changes that are taking place at FDA and (hopefully) helpful interpretations of regulations and guidance documents. Future posts will include an analysis of Bioresearch Monitoring Warning Letters. For example, have people been noticing the large increase in Warning Letters issued by CDER/Division of Scientific Investigations in the past two years or so?”

Time marches on and the focus of the blog has moved towards trying to craft some meaningful perspectives for GxP professionals and members of the public who are interested in commentary on the life science industry, clinical trials, and (of course) FDA.

GxP Perspectives: I’m going to make a few more changes to the blog in the next few weeks and soon will be including guest commentaries by GxP professionals on different aspects of our business. What I don’t know could fill a book (maybe two) and I want to hear from others on the practical issues that we face, such as electronic medical records, GLP issues, pharmacovigilance, interpreting guidance documents, and just what belongs in a trial master file. If you are interested in submitting a guest commentary, just add a comment indicating your interest and I will get back to you. (WordPress provides me with the email of anyone who comments which is not made public.) I am interested in hearing what you have to say.

I’ve also started inserting some photos and graphics, we don’t want the Blog to be too boring.

The stature of Peter Pan, London, one of the blogster's role models:)

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Blogroll: For those of you interested in the financial aspects of our industry – and others – Check out Hedge Hodge at:

http://www.hedgehogs.net/

FDA Warning Letter on Informed Consent

A new FDA Warning Letter shows the concern regarding the informed consent process that FDA has, along with most of us involved with clinical trials. This is a top FDA enforcement issue. However, are standard operating procedures (SOPs) the way to ensure GCP regulatory compliance at clinical trial sites?

Informed Consent of Research

In a letter dated 28 January 2010 to a clinical investigator at the Women’s Hospital, affiliated with the University of Michigan Health System, FDA’s Division of Scientific Investigations (DSI) at the Center for Drug Evaluation & Research raise some serious concerns regarding the informed consent process in several clinical trials for Cystic Fibrosis (CF).

CF is a devastating inherited disease with a juvenile onset that attacks the lungs and digestive systems of about 30,000 juveniles and adults in the United States. The impact on families who have a child with CF is dramatic with the lives of the entire family changed forever as they take steps to care for their children. CF patients and their families meet my personal definition of a “vulnerable population.”

I believe that clinical trials studying CF need special protections for the young participants and their families.

That is why this FDA Warning Letter is so disturbing. These are not studies for male pattern baldness or another minor indication. They are for very sick children and young adults. Although the FDA citations seem a bit “technical” at first, it is very important that full disclosure of research is included in the informed consent process.

The Belmont Report

It is of particular concern that these studies took place at a very prominent health system; the Women’s Hospital is affiliated with the University of Michigan, Ann Arbor. The informed consent forms were IRB approved (the Warning Letter does not state which IRB). However, the informed consent of research study participants is a cornerstone of ethical research in the United States and much of the world. In 1979 the

Informed consent is a process

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued the Belmont Report, the key document published by the United States Government on research ethics. The report states:

“Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement to protect those with diminished autonomy.”

The violations documented by FDA include the failure to use language the sponsor requested to indicate a clear statement of research, a required element of informed consent (the sponsor requested changing the wording from “new drug” to “investigational or experimental drug”). In addition, the original approved informed consent form did not correctly state the purpose of the study originally stating the purpose was to see if the drug could “stop PA” (Pseudomonas aeruginosa). The wording should have been to “assess the safety and efficacy of a 28-day treatment… (to treat CF)” This is not a minor difference and there are more violations.

Standard Operating Procedures (SOPs)?

Shoud we require SOPs?

First, we need to clear: There are no regulatory requirements for SOPs at clinical sites. None. The clinical investigator offered some corrective actions that included writing SOPs about the informed consent process. FDA seemed to believe that SOP changes could be a satisfactory corrective action. They say:

“Your corrective actions to this finding included the development of new standard operating procedures (SOPs) including: ‘Completing the eResearch Application’ to ensure that a member of the study team reviewed the consistency of the information in the protocol, investigator’s brochure, consent document and the eResearch submission; ‘Responding to Monitoring Reports’ which required prompt response to any observations and a formal report to the IRB for further consideration; and ‘Obtaining Informed Consent’ which will prohibit handwritten statements on the informed consent form.”

FDA stated that the response was inadequate but later in the Warning Letter they say that another SOP would, “serve as corrective actions to prevent the recurrence of this finding” (to ensure that the investigations were conducted according to the investigational plans).

A Question of Training.

I have a different perspective. I think that the informed consent violations raise a genuine concern on how well the informed consent process and the principles of the Belmont Report are being taught to clinical investigators and IRB members involved in biomedical research at UM and the Women’s Hospital. To me, this

GCP Training

is a question of being “qualified by training and experience,” and can’t be fixed with an SOP. For example, the primary method of training researchers at the University of Michigan, and a lot of other institutions, is through web-based training initiated by NIH. Web-based training is OK as a supplement to other training but ultimately a researcher needs to interact with others and have the opportunity to ask questions and be involved in problem solving discussions. Any reasonably bright individual is going to be able to breeze through a web-based training module and will retain very little.

We are placing a lot of administrative burdens and demands on both IRBs and clinical investigators. These demands take time and resources away from Good Clinical Practice. Investigators are being asked to sign and date reams of paper that could be delegated to the appropriate staff member. IRBs are asking for more and more documentation in an effort to comply with the requirements of FDA’s Bioresearch Monitoring program and other federal requirements. In fact, the University of Michigan had a simple checklist study halted because of bureaucratic interference. See this op/ed piece authored by the American Enterprise Institute, which accurately highlights some of the problems. I don’t agree very often with AEI but in this case they make a good point:

http://www.aei.org/article/100868

I would suggest that it is far more important to get “Back to Basics.” This includes research protocols that make sense and are practical in a clinical setting. It means emphasizing what is significant in protecting the rights, safety, and welfare of clinical trial participants (not the trivial). Finally it means ensuring that the data generated by a clinical trial can “stand alone” and be verified by regulatory authorities. Good, solid recordkeeping. I am not convinced that instituting SOPs at clinical research sites is the way to do this.

Here is a link to the Warning Letter:

http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm199751.htm

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Reflecting on the Trial Master File, the TMF

Post updated 28 January 2011: Just what is a trial master file or TMF? What are “Essential Documents?” How does FDA expect to see researchers document a clinical trial? Are there differences between FDA and EMA, the European Medicines Agency in TMF requirements? UPDATE: Read the Final version of the “EMA Reflections” Document on EDC, released after this post was originally published.

Documentation Requirements for Clinical Trials

It is interesting to note that although “TMF” is a standard industry term in the United States and is used by regulators around the world, the FDA doesn’t actually have a TMF inspection and rarely uses the term. FDA regulations are vague about the exact documents required for a clinical trial. In a response to an inquiry about documents answered by “GCP Questions,” a program within the Office of the Commissioner, FDA stated on 02 November 07:

“FDA’s regulations are intentionally pretty general, the reason for this is that the agency believes that sites and sponsors should have the necessary flexibility to adopt procedures that will comply with the regulatory requirements, and make sense (given the complexity of the study and available staff), without being unnecesarily burdensome.”

While this may be a commendable intent, it isn’t particularly helpful. I understand that regulations and guidance documents can’t be overly specific, but vague guidance on regulatory compliance leads to what I call, “regulation by rumor.” People will use an anecdote they have heard about what they think an FDA investigator wants in order to determine what documents FDA considers essential to a clinical trial. This can cause real problems between a clinical site and a monitor or auditor. There are genuine differences on how to document protocol deviations and other issues.

The term “trial master file” comes from the ICH E6 Guidance Document on Good Clinical Practice (E6). (Links to E6 and other documents related to this post are listed at the conclusion of the post.) Section 8 of E6 is called, “Essential Documents for the Conduct of a Clinical Trial.” In the introduction to Section 8 the Trial Master File is discussed. I consider E6 to be the authoritative document on the subject. Section 8 has a comprehensive list of Essential Documents, their location and what is necessary before, during, and after a clinical trial. When I define “TMF” I use the documents listed in Section 8 as my primary guidance. The only significant addition to this list (that I am aware of) is the FDA requirement for a Final Report, from the investigator to the sponsor. (I have an article on Final Reports at the conclusion of this post.)

ICH E6 Sets the Standard for Essential Documents

However, some regulatory authorities don’t seem to be emphasizing E6 as much as they may have in the past. It has been suggested that there might be additional “Essential Documents” although no regulatory agency that I know of has published a comprehensive list that could complement E6. Also, it has been suggested that there may be a “Good Clinical Practice” standard other than E6. FDA stated this when they rewrote the requirements for Foreign Clinical Studies Not Conducted Under an IND (21 CFR 312.120). Where you can find an alternative GCP isn’t discussed.

I think that E6 gives sound recommendations for GCP compliance. We should be using it more, not less. It has been published in the Federal Register as official FDA Guidance. It is the only guidance that FDA has on the TMF.

When discussing the TMF one of the trickiest issues involves electronic records, including electronic medical records (EMRs) at a hospital or medical center. There is a lot of grey area as far as protecting privacy, access to EMRs, and the validation of an institution’s EMR system. Unfortunately there isn’t a definitive guidance document on the topic of EMRs. FDA does have a guidance document on “Computerized Systems Used in Clinical Investigations.” It is found in the Important References section on your right, along with E6. Another resource that I recently became familiar with is a document from EMEA with the clever name of “Reflection paper on expectations for electronic source data and data transcribed to electronic data collection tools in clinical trials.” I’ve attached a PDF copy for your viewing pleasure at the bottom of the post. It contains some excellent recommendations. (Also attached is the final document released after this post was originally written. It is very similar: See “EMA Reflections”)

Electronic Medical Records

The “Reflections” document discusses Assigning Responsibility for maintaining clinical trial records. FDA regulations assign responsibility to either the sponsor or the clinical investigator. The “Reflections” document notes that the clinical site needs to maintain control over source documents and not hand over the responsibility to a sponsor. Source documents are the responsibility of the clinical investigator. This includes worksheets or standardized forms that a sponsor might prepare for a site in order to conduct the study according to the protocol. Even though the worksheets are written by the sponsor, they become the Responsibility of the Investigator. Lately FDA has taken to making this point on Warning Letters. Here’s an example from a recent FDA Warning Letter to a clinical investigator on the subject of “adequate and accurate subject case histories.”

“Your site chose to use the sponsor’s standardized forms as source documents to record and document information related to the subjects’ study visits. Per the standardized form, your site was to “Complete the Inclusion/Exclusion Criteria Worksheet to evaluate for study eligibility.” In the FDA investigator’s review of 16 of 65 subject records at your site, there was no Inclusion/Exclusion Criteria Worksheet found for any of these subjects.”

Notice FDA's Wording in Warning Letters

Notice that FDA considers that the site “chose” to use the sponsor’s forms. These records are the responsibility of the clinical investigator. As such, if there is a problem with them during an FDA inspection, then the problem belongs to the clinical site. In this case, the problem was significant enough to result in a Warning Letter. Having solid documentation of a clinical baseline, including recording the Inclusion/Exclusion Criteria are Very Essential Documents. It should be noted that this clinical investigator had a lot of additional problems, not just the sponsor’s standardized forms, or worksheets.

The EMA “Reflections” document gives some good advice for clinical trial recordkeeping. They use the old FDA guidance ALCOA- Attributable, Legible, Contemporaneous, Original, and Accurate and add four additional elements. They are Complete, Consistent, Enduring, and Available When Needed. The last point is particularly important. If you can’t show the document to a regulatory inspector, then for the purposes of the inspection, it doesn’t exist. I would add one additional element; QUALITY. People sometimes place importance on fax coversheets, which are not Essential Documents, instead of the quality of the source documents that document a clinical baseline and protocol-required activities.The quality of the documents used to support an application for a new drug or medical device is sometimes overlooked, to the detriment of Good Clinical Practice. These are the documents used to protect human subjects in research and ensure data integrity. Their quality should allow them to “stand alone.”

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—-
Updates posted 28 JAN 2011- Read about the Academy of Medical Research Report by Nick Taylor in Outsourcing-Pharma

UPDATE 28 JAN 2011: There is a very interesting Important Notice to IRBs that is on the FDA website. Sort of a Coast IRB redux.

UPDATE 6 January 2011: Two Important New GCP Documents:

There is a Draft Guidance on Electronic Source Documentation in Clinical Investigations. The comment period is for 90 day (April 4, 2011 ?)

There is a new Final Rule on required elements of Informed Consent. You can read the Federal Register Announcement here that includes FDA comments in the preamble. The exact change in 21 CFR Part 50 is:

“Sec. 50.25 Elements of informed consent.

* * * * *
(c) When seeking informed consent for applicable clinical trials,
as defined in 42 U.S.C. 282(j)(1)(A), the following statement shall be
provided to each clinical trial subject in informed consent documents
and processes. This will notify the clinical trial subject that
clinical trial information has been or will be submitted for inclusion
in the clinical trial registry databank under paragraph (j) of section
402 of the Public Health Service Act. The statement is: “A description
of this clinical trial will be available on
http:[sol][sol]www.ClinicalTrials.gov, as required by U.S. Law. This
Web site will not include information that can identify you. At most,
the Web site will include a summary of the results. You can search this
Web site at any time.”

References:

Update: Read the Final Reflections Paper from the European Medicines Agency on Electronic Data Capture:

EMA Reflections

Also: There are a couple of very good comments to this post by experienced professionals. They are well worth reading.

Here is the E6 document:
E6_ICH_GCP

Here is the FDA guidance document on “Computerized Systems Used in Clinical Investigations.”

Here are some links that will be of use in researching original data and certified copies:

Compliance Policy Guide 130.400 (equivalent to 7150.13)

Applied Clinical Trials: CDISC Clinical Research Glossary

And finally on Notes to File:

http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/article/articleDetail.jsp?id=500437

Please remember, your comments, questions, complaints, and advice are always welcome !!!

++++In news from GxP Perspectives++++

Announcement: The 18th and 19th of January 2011 I will be at the conference for Developing CAPAs in the GCP Environment, Arlington, VA. And Again in 2012!

2012 CAPAs in the GCP Environment

Read the updated article on the Form FDA 1572 in:

Applied Clinical Trials “Closing Thought” on FDA 1572

ALSO: Please join me on LinkedIn at:

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Read additional posts on Good Clinical Practice- GCP:

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FDA Budget Asks For $4,030,000,000

FDA has requested $4.03 Billion, a 23% increase, for fiscal year 2011. (I hope I got all the zeros right.) This would be the largest budget in FDA history. Much of the increase is for the new tobacco program. The largest chunk is for food safety and we have an analysis of that by Sid Olufs, the blog’s resident book reviewer and food safety analyst.

However, the issue of the FDA budget request has been lost in the light of the deficit and other news. On the Blogroll FiercePharma, but not FierceBiotech, comments as well as Gooznews on Health. Before we get to Sid’s comments I have a few short, but important items to report. First, here is the FDA press release on the budget:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm199516.htm

UPDATE: This Sunday, the 18th of April, the Pew Research Center released a devastating report on the decline in confidence in government over the past 12 years, including a 17% decline for FDA. Pew says, “The declines have been particularly large for the Department of Education, the FDA, the Social Security Administration, as well as the EPA, NASA and the CDC.” Ouch.

(Original Post):

This Sunday, the 7th of February, is the 10th National Black HIV/AIDS Awareness Day and February is Black History Month. Although African-Americans are only 13% of the U.S. population, they have nearly 50% of the newly diagnosed cases of HIV/AIDS. Here is a statement by Dr. Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Disease that conducts AIDS research world wide:

http://www3.niaid.nih.gov/news/newsreleases/2010/BAAID10.htm

Finally there is an interesting “Frequent Flyer” column in the business section of the NY Times. It is written by a retired physics professor, Robert Kolenkow, who is a diabetic. I am a Type 1 diabetic and a very frequent flyer. I have Travel Too Much status with Alaska Airlines (They call it, “MVP Gold”). I have always found it challenging to manage my diabetes on board a packed coach cabin going across the country so I was interested in what Professor Kolenkow had to say. He participates in a diabetes mentoring group called A1C Champions. They are sponsored by Sanofi-Aventis. Since I use Sanofi insulin I am not sure how happy I am about this. However, you can take a look and judge for yourself.

Here is a link to A1C Champions:

http://www.a1cchampions.com/

Here is a link to the article:

http://www.nytimes.com/2010/02/02/business/02flier.html?ref=todayspaper

Guest Commentary by Sid Olufs:

Paying for a Difficult Job

In an earlier post I briefly described the ambitious agenda facing the new Deputy Director for Food, Michael R. Taylor (FDA Has a New Look for Food). It included these lines describing his responsibilities: “inspection and ensuring compliance with rules, coordination with state and local agencies who do much of the work of food safety, responses to “incidents” that hurt people, getting a handle on imported items that find their way into food, sponsoring and organizing the scientific and technical research needed to design a safe food system, including animal feed and veterinary care, and building the information network that helps to knit all of these together.”

Others have looked at the costs of building a food safety system that can do all of this adequately. In the most comprehensive outside analysis of FDA responsibilities and capacity, the authors concluded that the FDA is critically underfunded in its science-based regulation and decision making, so much so as to put public health at risk. (FDA Science and Mission at Risk, Report of the Subcommittee on Science and Technology, Prepared for FDA Science Board, November 2007.) The Congressional Budget Office estimate of the costs of implementing HR 2749, which falls short of the more complete goals of FDA Science and Mission at Risk, came to almost half a billion dollars a year for the first few years of transition, and about a billion dollars per year thereafter. (CBO Cost Estimate, h.r. 2749, July 24, 2009.)

The Obama administration has now released its budget for FY2011. As described in more detail in the agency budget documents submitted to Congress, FDA requested about $220 million in the form of fee-based inspections, plus additional spending over current spending which brought the total food system upgrade request to about $318 million in additional money for 2011. See the attached link for a brief summary:

http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/BudgetReports/UCM199447.pdf

I spent a little time looking at the documents, and only found about $290 million in budget increases in the documents released by OMB. See their detailed HHS budget description, at:

http://www.whitehouse.gov/omb/budget/fy2011/assets/hhs.pdf

The first three pages are the FDA budget summary (the pagination starts at p. 461).) You will see the $220 million on 09.02 Food Registration and Inspection User Fee, on the third page (page # 463) of this document. The fees are “proposed.”

I found no separate discussion of the resources devoted to upgrading the FDA’s information technology, a critical resource in the needed upgrades. It could be that a separate item is included for this, but I searched in vain in the detailed agency appendices and in the Analytical Perspectives that accompany the Budget.

Judging just by the number referred to here, it does appear the Obama administration is taking food seriously, at about two-thirds to three-quarters of the resource level implied by the panel of experts that assembled FDA Science and Mission at Risk. I for one will find it interesting to read how far down that road this new budget authority will take us.

By Sid Olufs

Blogroll Pick: Gooznews on Health– With every post, I am trying to highlight one of the blogs on the Blogroll to your right. This time Gooznews has some interesting comments on the FDA Budget requests.

http://www.gooznews.com/

REMEMBER, YOUR COMMENTS ARE ALWAYS WELCOME !!!

You can read additional posts on FDA Commentaries here:

https://carl1anderson.wordpress.com/category/fda-commentaries/

You can read additional posts on Food Safety here:

https://carl1anderson.wordpress.com/category/food-safety/

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Blogroll: For those of you interested in the financial aspects of our industry – and others – Check out Hedge Hodge at:

http://www.hedgehogs.net/

Economists, Technology, & Clinical Trials

God bless Joseph Stigltz. There is a brief interview with him in the Sunday NY Times Magazine by Deborah Solomon, “Questions for Joseph Stiglitz.” There is a link at the bottom of this post. I have only started paying close attention to what economists have to say in the past few years. This certainly intensified when all hell broke loose in the fall of 2008. Joseph Stiglitz, a professor at Columbia, is a Nobel prize laureate and a very smart man. He also has a dry wit that I find quite funny (some people have doubts about my sense of humor) and I have just ordered his new book, “Freefall: America, Freemarkets, and the Sinking of the World Economy.” I definitely want to know what he has to say about it all.

Prioritize ???

However, what really caught my attention and led me to write this post is one of the last questions Solomon had for Stiglitz when she asked, “By the way, when I tried you on your cell phone, a voice said, ‘This is the number for Joseph Stiglitz, but he doesn’t check his messages.'” His response? “I just never figured out that part of the cellphone.”

This blog isn’t about economists, its about the regulation of health products by FDA in general and about clinical trials in particular. Clinical trials are very expensive to conduct. In addition, the massive amounts of recordkeeping involved leads to routine mistakes and the destruction of a great many trees. There has been a big push towards electronic medical and regulatory records, electronic case report forms and technology in general. This has generated discussion and debate about how these records should be regulated and whatsteps we need to take. FDA’s initial effort to regulate computerized systems, Part 11; Electronic Records, Electronic Signatures, was met with sharp resistance from industry and enforcement has been scaled back considerably as FDA utilizes “enforcement discretion.” However, most of us understand that these systems need to be dependable and that means, in some way, shape, or form, that they be “validated.”

Unfortunately what I see a lot is that the quality of the system used to maintain records is considered more important than the quality of the actual records that contain the data used to approve new drugs and medical devices. Some folks seem to forget that technology is a means to an end (full disclosure: I am not very tech savvy). As a result, we have seen an increase in the number of FDA enforcement actions. FDA Warning Letters to clinical sites have skyrocketed in the past few years. And in my viewpoint one of the major reasons is the poor quality of clinical trial protocols and recordkeeping. Sometimes you need to take a look at the basics of what you are doing.

Which brings me back to Joseph Stiglitz. Here is a very smart man who is engaged with problem solving. Very Big Problems that impact us all. Yet he doesn’t know how to check his voice mail. As far as I’m concerned, its a question of knowing priorities. Just stop and think about which is a more important activity; understanding the complex economic issues that caused the Wall Street meltdown, or playing with your Blackberry? I appreciate the Stiglitz approach.

Here is a link to the Stiglitz interview by Deborah Solomon:

http://www.nytimes.com/2010/01/31/magazine/31fob-q4-t.html?ref=todayspaper

REMEMBER, YOUR COMMENTS ARE ALWAYS WELCOME !!!

Blogroll Pick: Paul Krugman’s Blog. I’m continuing to list a site on the Blogroll (to your right) each time I publish a post. As long as we are on the topic of economics why don’t we take a look at what another Nobel laureate has to say? Find it on the Blogroll along with a number of other interesting places to visit. Have fun.

http://krugman.blogs.nytimes.com/

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