FDA Warning Letters to International Companies for CAPAs & Complaints

November 28, 2010

FDA warning letter CAPA complaint

Warning Letters for CAPAs & Complaint Investigations

In the past 90 days FDA issued five Warning Letters to international firms for GMP failures to adequately investigate complaints. Whether it is GMPs, GCPs, or GLPs FDA is making the case that when things go wrong, it is a company’s responsibility to investigate and implement the necessary corrective and preventative action (CAPA), In the past, FDA was hesitant to issue Warning Letters to firms outside the United States. That clearly is changing as both the Center for Devices and Radiological Health (CDRH) and the Center for Drug Evaluation and Research (CDER) have issued Warning Letters to companies in Canada, Switzerland, China, Sweden, and India. Although the companies are from diverse locations and range from medical devices, active pharmaceutical ingredients (APIs), and finished pharmaceuticals, one issue connects them all: the failure to adequately address complaints. For the medical device Warning Letters, corrective and preventative actions (CAPAs) figured prominently.

FDA first opened international offices in 2008 in India and China and now has offices in Europe and Latin America as well. The international offices are predominantly focused on GMPs for food, drugs, and medical devices. FDA has also stepped up its inspections of clinical trials in international locations including Russia and Eastern Europe. However, there has not been the corresponding surge in Warning Letters. At least not yet. Here are charges that FDA made in the international Warning Letters:

CAPA complaint FDA warning letter

Failure to Investigate Bacterial Contamination

Claris (India): On April 15, 2010, your firm received a complaint from a U.S. distributor (Sagent Pharmaceuticals) informing you that Metronidazole Injection USP IV bags (lot A090744) were contaminated with a informing you that Metronidazole Injection USP IV bags (lot A090744) were contaminated with a swirling mass, which the complainant identified as the fungus Cladosporium species. There is no information in the Complaint Investigation Report to show that Claris initiated an investigation to determine the root cause and extent of the problem until April 26, 2010, when Claris received this contaminated large volume parenteral and examined it.

Storz Medical (Switzerland): Failure to establish and maintain adequate procedures for verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). For example, no protocol, including acceptance criteria, was established for the validation of Change Request (b)(4). Additionally, there was no documentation showing that this change was validated. The change was implemented to fix cracked cooling pumps in the Modulith SLX-F2.

The Warning Letter goes on to say:

international complaint investigation failure FDA

Failure to Establish Procedures for Complaints

Failure to establish and maintain adequate procedures to ensure that any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications shall be reviewed, evaluated, and investigated unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c).

Neoventa Medical AB (Sweden): 1. Failure to establish and maintain adequate procedures for implementing corrective and preventive action that include requirements for verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device and that all activities required under this section and their results be documented, as required by 21 CFR 820.100(a)(4) and (b).

2. Failure to establish and maintain adequate procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a).

Once again the direct connection between the failure to investigate complaints and the failure of a system of CAPA.

FDA Warning Letters CAPA

Chinese API Manufacturer Hit with FDA Warning Letter

Yunnan Hande (China): Failure to thoroughly investigate complaints for APIs batches that do not meet the United States Pharmacopeia (USP) compendial requirements that may have been associated with the specific failure or discrepancy. In addition, your investigation was not extended to other batches that may also be affected.

Pega Medical (Canada): Failure to establish and maintain the requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR 820.50(a)… For example, Complaint NCR No. (b)(4) reported…”

Read the Warning Letters:

Storz Medical, AG Warning Letter

Yunnan Hande Biotech Warning Letter

Claris India Warning Letter

Pega Medical Warning Letter

Neoventa Medical AB

FDA International Resident Posts

And What About Clinical Trials?

At a recent FDANews conference FDA representative Ann Meeker-O’Connell, M.S., Division of Scientific Investigations, Office of Compliance CDER/FDA, said,

FDA warning letter international complaint investigations

Clinical Trial CAPAs Face Different Challenges

“But, clinical trials are inherently variable systems with a goal of producing reliable data for regulatory decision-making . . . How can this be reconciled with a quality system framework originating in mass manufacturing?”

That is a very good question and one that many of us have been wrestling with. However, it is clear that FDA has been taking on the question of the international nature of the drug and device industry, including manufacturing and clinical trials.

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Read about the Academy of Medical Research Report by Nick Taylor in Outsourcing-Pharma

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

Public Comment Period is Open for New FDA Draft Guidance:
FDA Draft Guidance on Electronic Source Data in Clinical Investigations


Visit the TMF Page at the Top Right of the Blog! I am trying to assemble resources for those of us concerned with the Trial Master File. I welcome any contributions you might have of interesting articles and resource documents.

On FDA’s Website there are Two New Warning Letters from FDA to Clinical Investigators that show the need to effectively respond to a Form FDA 483, Inspectional Observations, with a well thought out CAPA Plan.

Response Letters to a Form FDA 483, Inspectional Observations

November 7, 2010

FDA 483 response

How Should You Respond to a Form FDA 483?

What is an adequate response to a Form FDA 483, Inspectional Observations? That question was discussed by two representatives of FDA at a training workshop hosted by the Pacific Regional Chapter of the Society for Quality Assurance and the Organization of Regulatory and Clinical Associates – Northwest. The workshop, held on 4-5 November 2010 in Seattle, featured discussions by Chrissy J. Cochran, PhD, from the Division of Bioresearch Monitoring (BIMO) at the Center for Devices and Radiological Health (CDRH) and Mihaly S. Ligmond, Consumer Safety Officer, Division of Domestic Field Investigations, Office of Regulatory Affairs (ORA). ORA is the field organization that conducts most FDA inspections. Both Cochran, who spoke by teleconference on the 4th, and Ligmond, who attended on the 5th, stressed the do’s and don’ts of responding to an FDA 483.

The Form FDA 483

Both FDA speakers stressed that the 483 is the preliminary observations of the field investigator, not the final compliance determination of the Agency. Both emphasized that there was no requirement to respond in writing to a 483. However, both told the training session that if there are issues identified on a 483, then a clear written response can help prevent enforcement action, including a Warning Letter, by FDA. Cochran discussed a few ineffective FDA 483 response letters received by CDRH. They included a clinical investigator who was using an informed consent form without all of the required elements required by 21 CFR 50.25. These elements include a clear statement of research; alternative procedures; a discussion of confidentiality and other important information. The clinical investigator complained that: “You cited us on a technicality.” This was a clear and significant violation of FDA clinical trial regulations and this was not an acceptable response.

Cochran gave an example of an adequate response to an FDA 483 for protocol violations. The response included a copy of a written procedure developed to prevent recurrence of the violation. The procedure was presented to a seminar for study staff with a sign-in sheet with the date of the seminar. It included implementation dates with a review scheduled after three months to determine the effectiveness of the corrective action.

The response to an FDA 483 should go to both the District Office and to CDRH, Cochran said. She stated that it is the assessment at BIMO that makes the final compliance determination for Bioresearch Monitoring inspections. She reviewed the issues that BIMO considers when reviewing an establishment inspection report (EIR) and a Form FDA 483, Inspectional Observations. These include:

• Are the FDA 483 observations actual violations of the regulations?
• Are there additional violations in the exhibits submitted with the EIR?
• Are the observations documented with exhibits or discussion in the EIR?
• Are the observations significant?
• Did the inspected party address the issue in their response?
• Is the response adequate? “We will carefully look at it.”

Ligmond, who is a National Expert for drug good manufacturing practice (GMP) inspections, gave the following recommendations for a response letter to an FDA 483:

• Set a reasonable timeline for taking action;
• Initiate a “Global Response” if the deficiency can impact other areas;
• Include details and attachments;
• Be comprehensive;
• Address disagreements with the observations;
• As a courtesy, copy the investigator

FDA 483

The FDA 483 is the Preliminary Observation of the FDA Field Investigator

Both Cochran and Ligmond restated the new FDA policy for written responses to an FDA 483 if the response is to be considered by FDA prior to issuing a Warning Letter. That response time is 15 business days from the date the FDA 483 is issued. Ligmond gave an excellent recommendation to avoid possible disputes on FDA 483 observations. “Address misunderstandings promptly, courteously, and with the facts,” he said. He discussed the importance of a daily wrap-up session o clear up any disagreements or inaccurate information that may have been given to the FDA field investigator.


Corrective and Preventative Action, or CAPA, was discussed by both speakers. Ligmond said that a CAPA plan should address problems completely and in a timely manner. Cochran said that a good CAPA plan should assess the root cause of deficiencies; identify the problems; evaluate the extent of problems; give a clear timeline, describe the CAPA being taken; and reassess the root cause.

Inspection preparedness was also discussed. Ligmond said to spend each day as if you were going to be inspected by FDA. They stressed the importance of Mock FDA Audits in preparing staff for inspections.

FDA 483 response

ALWAYS Respond to a Form FDA 483

My own experience is that it is always a good idea to respond to an FDA 483. If there is a problem, then give clear details on how the problem is going to be fixed, with specifics such as a timeframe. If you disagree with the observation, then follow Ligmond’s advice to address it “with the facts” and with documentation of the facts. FDA rarely will accept excuses such as “I thought my study coordinator was going to do that.” However, if there is a legitimate response, you should make it in a clear, respectful manner. The 483 responses I have worked on always included specific actions, specific dates, and a specific person or department accepting responsibility for ensuring that the corrective action takes place. And they always include documentation of corrective actions. If it isn’t documented, then it’s just a rumor.

A new feature from FDAzilla on FDA 483s

Read the Press Release on 483s


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FDA Clarifies Adverse Event Reports for Clinical Trials

October 10, 2010

FDA adverse event reporting

FDA Final Rule Clarifies
AE Reporting for
Clinical Trials

On 28 September 2010 FDA announced that it was issuing a final rule that clarifies safety reporting for adverse events during clinical trials. The final rule impacts drug and biologic regulations for clinical trials conducted under an investigational new drug (IND) application (21 CFR 312) and bioequivalence studies (21 CFR 320). The draft rule was published in 2003 and received numerous comments. These comments, combined with increased concern over drug safety, led to significant changes by FDA. The new rule defines the separation of clinical trial safety adverse event reports and post-market safety reporting. The agency is working on new regulations for post-market safety reports. FDA stated that the separation was necessary to improve the quality of safety reporting, monitor the safety of drugs and biologics, and harmonize adverse event reports internationally. There are some significant differences between the draft rule of 2003 and the final rule published on 28 September 2010 including:

Replace the defined phrase ‘‘associated with the use of the drug’’with the term ‘‘suspected adverse drug reaction (SADR),’’
• Require submission of expedited reports of ‘‘information sufficient to consider product administration
• Make it clear that safety reports of overall findings or data in the aggregate must be submitted in a narrative format,
• Permit the determination that an SADR is life-threatening to be based on the opinion of either the investigator orsponsor (as opposed to only the investigator),
• Require that the sponsor notify FDA and all participating investigators of each SADR that is both serious and unexpected, based on the opinion ofeither the investigator or sponsor (asopposed to only the sponsor),
• Require a ‘‘minimum data set’’ for each report of an SADR submitted toFDA, and
• Clarify the sources of information that sponsors must review for safety surveillance and reporting purposes.

FDA clarifies adverse events clinical trials

FDA Adopts ICH E2A Definitions

Perhaps the most significant change in the final rule is that FDA is adopting the terms and definitions in the ICH guidance document E2A that are used throughout the world. Prior to issuing the final rule FDA regulations did not specifically define the term “adverse event” although the term was referred to repeatedly in the regulations and there was a definition for “serious adverse event.” Using the ICH definitions will make it easier for clinical trial professionals to “speak the same language” when conducting research. As FDA clarifies definitions, communications between sponsors and investigators should become easier. Hopefully, researchers will now understand that it isn’t necessary to “report all SAEs immediately.” FDA is stating clearly that:

“… the revisions to the IND safetyreporting requirements will improve theoverall quality of safety reporting andthe agency’s ability to review critical safety information by ensuring that theinformation that FDA receives in an INDsafety report is relevant and useful.

Under former regulations, there may have been over-reporting of serious adverse events for which there was little reason to believe that the drug had caused the event, complicating or delaying FDA’s ability to detect a safety signal.

In this final rule, FDA clarifies definitions, provides examples of the types of evidence that suggest a causal relationship for purposes of reporting asuspected adverse reaction to the IND and participating investigators, and revises the requirements for expedited reporting of serious and unexpected suspected adverse reactions to the IND.”

The ambiguity over reporting adverse events has caused friction between many study coordinators and CRAs. Hopefully, FDA clarifying AE reporting will help researchers focus on issues of significance.

FDA Announcement of Final Rule

At the same time FDA issued a draft guidance on Safety Reporting Requirements which will be the topic of a future post. The comment period is OPEN!

Safety Reporting Requirements for INDs and BA/BE Studies

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

clinical trials adverse event FDA

TMF Webinar on Thursday, 14 October 2010

Special Announcement: TMF Webinar 14 October

Read the updated article on the Form FDA 1572 in:

Applied Clinical Trials “Closing Thought” on FDA 1572

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FDA Sends J & J a Warning Letter For Internet Marketing- Forest Labs Agrees to Pay $300 Million for Violating FDA Laws

August 30, 2010

website FDA Warning Letter J&J

internet Marketing Cited in FDA Warning Letter

Johnson and Johnson subsidiary, DePuy Orthopedics, received an FDA Warning Letter for marketing violations. The Warning Letter cites DePuy for internet marketing of their products without FDA approval. The Warning Letter is one more headache for J&J that is discussed in the post from 19 August on J&J’s Quality Control Headaches. The Warning Letter states:

“The Office of Compliance (OC) in the Center for Devices and Radiological Health (CDRH) reviewed your website, http://www.depuyorthopaedics.com. for the TruMatch™ Personalized Solutions System and the Corail® Hip System.”

Read the Warning Letter to DePuy

View J&J’s Current Webpage on Hip Replacements

UPDATE: J&J is not the only company in hot water with FDA for marketing. Forest Laboratories has agreed to a $300 Million settlement for the following: “Forest Pharmaceuticals, Inc. entered into a plea agreement in which the company accepted responsibility for criminal actions including distribution of an unapproved new drug, distribution of a misbranded drug, and obstruction of an FDA inspection.”

FDA Press Release on Forest Labs

Read “J&J’s Quality Control Headaches”

On The Blogroll: Again, I would like to highlight some of the blogs found on the blogroll to the right. This blog focuses on public health, The Pump Handle.

Save The Date: On 4-5 November 2010 the Pacific Regional Chapter of the Society for Quality Assurance (PRCSQA) and the Organization of Regulatory and Clinical Associates (ORCA), a Pacific Northwest based organization, will co-sponsor a Fall Training on regulatory compliance topics in Seattle, WA.

The PRCSQA LinkedIn Group will update the agenda for the training. PRCSQA Fall Training workshops have traditionally been “at cost” and are an affordable training opportunity. The sessions will cover both GCPs and GLPs with speakers lined up on vendor management, quality systems, and GLP updates.

In news from GxP Perspectives read the updated article on the Form FDA 1572 in:

Applied Clinical Trials “Closing Thought” on FDA 1572

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FDA Announces 21 Draft Proposals to Increase Transparency

May 25, 2010

FDA announced the Phase II report on their effort to increase transparency stating:

FDA Announces Transparency Report

FDA Seeks Public Comment on Transparency

On May 19, 2010, the Transparency Task Force released a report containing 21 draft proposals about expanding the disclosure of information by FDA while maintaining confidentiality for trade secrets and individually identifiable patient information. FDA is accepting public comment on the content of the proposals, as well as on which draft proposals should be given priority, on this website until July 20, 2010.

The FDA Report on the 21 Draft Proposals is available in PDF format.

The Blog will be reading the report carefully and urges you to do so as well.

UPDATE: In other news of interest FDA’s Principal Deputy Commissioner, Dr. Joshua M. Sharfstein, testified to Congress about the recall of adulterated Tylenol and other pediatric medicines. The New York Times reported that FDA is considering additional penalties including the possibility of criminal prosecution.


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FDA to Increase Criminal Prosecutions

March 7, 2010

FDA plans to increase the number of criminal prosecutions by the agency along with other measures to curb criminal violations of the Food, Drug, and Cosmetic Act. These aren’t intended for your every day criminal. instead, FDA wants to go after top officials in regulated industry. In my previous post I discuss FDA proposing new regulations for reporting the falsification of research data in the first significat rule change regarding clinical trials by the new FDA leadership. It seems that FDA’s leadership is focused on

criminal prosecutions and FDA

Should FDA Focus on Criminal Prosecutions?

expanding its use of the criminal jurisdiction FDA has had for decades. According to Alicia Mundy in the Wall Street Journal:

The Food and Drug Administration plans to increase prosecutions of pharmaceutical and food industry executives as part of an effort to refocus its criminal division, which has been under attack in Congress and is criticized in a new government report.”

The Office of Criminal Investigations

The Office of Criminal Investigations (OCI) is technically part of the FDA’s field organization, the Office of Regulatory Affairs. However, there is little contact between the field employees that conduct Bioresearch Monitoring and other regulatory inspections and the criminal investigators of OCI. During the 13 years that I worked in ORA after the criminal group was formed I met an OCI official only once. She was a former Secret Service officer and a very smart professional. However, she did not have extensive knowledge about clinical trials, which is why we met. FDA seems to want to improve the relationship between OCI and the rest of the Agency. The Government Accountability Office (GAO) issued a critical report regarding OCI to Congress last Thursday, March 4th. Responding in a letter to Congress FDA stated it wanted to:

FDA office of criminal prosecutions

FDA Office of Criminal Investigations

improve procedures for information-sharing between OCI and other Agency components with the goal of enhanced allignment of criminal/regulatory priorities and activities.”

The FDA letter also mentions increasing the “appropriate use of misdemeanor prosecutions” the item that has gotten most of the attention. This seems like a good idea and I’m all for prosecuting people who submit false data and commit other crimes. People who commit crimes are called criminals and white collar criminals have been neglected all too often. The letter also discusses the debarment of clinical investigators. The last item mentioned by the letter hasn’t received very much press attention when it states:

“Finally, the committee recommended that FDA improve the coordination of its response to cargo theft of FDA-regulated products, such as pharmaceuticals and infant formula. Potential threats include counterfeiting, diversion, tampering, adulteration, misbranding, theft, and terrorist acts.”

That sounds like serious stuff. I’m not sure that I consider FDA the right federal agency to take on all of that, but I’m a regulatory consultant, not a criminal one. FDA has limited resources, even with the

FDA criminal prosecutions

Is FDA the right agency to pursue cargo theft of pharmaceuticals?

proposed increase in funding (see previous post). On one hand these developments seem that they are addressing critical needs.

On the other hand, FDA is a Public Health and regulatory agency and the regulation of critical industries, such as banking, insurance, food, transportation, and pharmaceuticals, has suffered in the past decade. Increasing criminal prosecutions may be a very good thing. But will it come at the expense of modernizing FDA’s other regulatory responsibilities? All too often public health has suffered due to an increase in funding for criminal prosecutions. I believe the primary focus of FDA should be a public health focus on the regulation of food, drugs, vaccines, and medical devices. FDA should look into updating regulations for clinical trials and other issues such as a recall authority for adulterated foods.

GxP Perspective:

FDA leadership has said, “In some cases, the agency may need to modernize existing standards in order to address ambiguities.” I would suggest that there are existing ambiguities in FDAs clinical trial regulations. There hasn’t been a substantive rewrite of the Investigational New Drug (IND) regulations since March 1987. This is an item that I consider to be of importance. There have been revisions of certain parts of the IND regulations, but we are basically working with regulations that are over 20 years old.

FDA regulations

Are FDA's regulations for clinical trials up to date?

Most clinical trial professionals I know are not criminals. They are dedicated, highly motivated, hard-working professionals who would like to do the right thing, if FDA would tell them. The IND regulations have overly vague specifications on what an “adequate and accurate case history” is and I can’t count the times people have asked me the requirements for source documents. Definitions for common industry and regulatory terms such as “trial master file” and “adverse event” cannot be found in FDA’s regulations.

In addition, the business of running a clinical trial has changed dramatically in the past 23 years. There has been an explosion of clinical trial vendors and outsourcing. The industry is qualitatively different than it was in the 1980s. It would be good if there was a concrete regulation telling a sponsor on how to provide oversight of a clinical laboratory or an eCRF vendor. I certainly am glad to see that FDA is taking on white collar criminals with increased criminal prosecutions. I think it is the right thing to do. I’m also in favor of federal law enforcement agencies, including FDA, taking on the problem of the theft of pharmaceuticals and infant formula. However, we also need to update the regulations for law-abiding researchers. I hope that Congress and FDA gives this some attention as well.

You can read the Alicia Mundy article here:



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FDA Proposed Rule on False Data

March 1, 2010

FDA has published a proposed rule, “Reporting Information Regarding Falsification of Data” in the February 19 Federal Register. FDA wants to require sponsors to submit reports to FDA about false data, or the possibility of false data, within 45 calendar days after the sponsor becomes aware of the information. The proposed rule is open for comment until May 20, 2010. (A proposed rule is an FDA proposal to change an FDA regulation.)

Sponsor Responsibility:

FDA states that sponsors are in the best position to determine if there has been falsification of data used in

FDA Proposed Rule

FDA Proposed Rule

clinical trials or in nonclinical (GLP) research. FDA notes that “through their monitoring, auditing, and reviewing of data,” sponsors can spot false data that FDA might not detect during a bioresearch monitoring inspection.

FDA issued the proposed rule because current regulations are unclear on the need to report falsification of data to FDA. The proposed rule states that sponsors are “reluctant or uncertain as to whether it is necessary to report the information (to FDA).” FDA notes that sponsors have excluded data of a clinical investigator suspected of data falsification or terminated their participation in a study without stating the reasons. FDA is concerned that persons suspected of data falsification then continue to participate in other studies. FDA states:

“Taking effective action in response to falsification could lessen the magnitude and impact of the falsification in a current study, reduce the potential for delays or compromise to other studies and applications (including studies and applications from other sponsors for whom such a person might also be working), and protect the rights, safety, and welfare of research subjects.”

FDA makes these comments in the “preamble” to the proposed rule. The preamble is FDA’s explanation of why the proposed rule is necessary with definitions and clarifications of those reasons. The preamble is followed by the actual proposed wording of the changed regulations.

A Closer Look:

Such a person” is nicely put, but the proposed rule doesn’t address whether clinical trial vendors are included in their concerns. There is not an actual mention of contract research organizations, clinical laboratories, IVRS vendors, eCRF systems, etc. There is a reference to, “any confirmed or possible falsification by any person involved in studies conducted by or on behalf of a sponsor or relied on by a sponsor.” FDA is very clear they want to include the possibility of falsification.

The proposed rule discusses the serious reasons FDA is concerned with the falsification of data. However, the

Propose Rule Falsification of Data

Falsified Data is a Roll of the Dice

distinct impression that I had from reading the proposed rule was that FDA is primarily concerned with the activities of a principal investigator at a clinical site. There is no discussion of the possible root causes of data falsification. During my career I have been asked to conduct “for cause” audits where data falsification was suspected. I primarily found a confused, undertrained staff member making unintentional mistakes.

Then there is the very real problem of overworked and/or undertrained staff deliberately altering data in an attempt to satisfy a supervisor and keep their jobs. This can happen not only at clinical sites or nonclinical laboratories, but at the many vendors participating in research that are seldom inspected by FDA.

GxP Perspective:

FDA asks, “How does a sponsor become aware of data falsification?” They offer a few brief examples including the “monitoring review and evaluation of study data (e.g., noticing unusual data on case report forms and/or analytical reports).” After issuing Warning Letters to J&J and ICON Clinical Research, Inc. (see previous posts) it is clear that GxP professionals working for sponsors need to develop the techniques necessary to determine fraud. FDA told ICON:

“Study monitors failed to identify that on multiple occasions, site personnel documented administration of study drug to different subjects at precisely the same time.”

FDA proposed rule

A Failure to Monitor?

Stop and think about this. It is entirely possible for monitors to review different charts at different visits andnot discover this possible fraud. When I conduct site audits I rarely compare things such as the time of administration of study drug across different charts. I usually review one chart at a time (maybe I should change).

These are issues that need review of data listings and biostatisticians who can look for funny numbers that aren’t necessarily evident to monitors and auditors (and FDA investigators). We need to utilize a variety of tools and not depend entirely on monitoring visits and site audits. One possible unintended consequence of this proposed rule is that clinical sites will be audited to the point it becomes a regulatory burden, not a safeguard for data integrity and the protection of study participants.

Consequences of Noncompliance:

FDA falsification dataIt is interesting to note that FDA asks, “What are the consequences of not reporting confirmed or possible data falsification?” The answer should be sobering. It includes the possibility of a violation of 18 U.S.C. 1001. You will note that Title 18 of the US Code is not specific to FDA. It is the section of Federal law that includes the basis for felony prosecutions. Tough stuff.

Request for Comments:

FDA offers definitions of falsification of data, a definition of “data,” and a definition of unintentional errors. FDA also explains why they consider 45 days to be appropriate and a number of other issues. The comment period is used to clarify and seek input for these definitions and issues of concern to stakeholders and the public. The proposed rule lists several ways to comment. This is an important proposal for changing FDA regulations for food, drugs, biologics, medical devices, and veterinary medicines. It is an attempt to address legitimate concerns for public health and consumer protection. It deserves our attention.

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