Infusion Pumps Receive FDA Attention in New Initiative

April 23, 2010

FDA attention to infusion pumps

New FDA Initiative on Infusion Pumps

FDA initiated a new effort to make infusion pumps, medical devices that deliver fluids including drugs, safer and more accurate. The initiative shows the attention that FDA is paying to patient safety. It includes a new draft guidance document released for comment. There have been a number of articles commenting about the infusion pumps that refer to “requirements” being issued by FDA. An example is from Medpage Today. There is a link at the bottom of the post to their article. However, this isn’t exactly the case. A “draft guidance document” is basically a preliminary recommendation. FDA is not issuing a “proposed rule” that would become a regulation that FDA can actually enforce. Please see the link to the Blog Compliance Zen at the bottom of this post that also discusses this issue.

This specific draft guidance document does in fact reference medical device regulations. However, it manages to use the words “recommend” and “must” (as in requirement) in the same paragraph describing information needed by FDA to evaluate the medical device:

infusion pumps FDA

Infusion Pumps are Necessary for Advancements in Diabetes Technology

“We recommend you identify your device by the regulation and product code described in Section 3, Scope. You must provide information on how your device is similar to and/or different from other products of comparable type in commercial distribution, accompanied by data to support the statement, as required by 21 CFR 807.87(f). Side by side comparisons, whenever possible, are desirable.”

These are some of the issues involved with developing an “Artificial Pancreas” that the blog has discussed in previous posts:

First Artificial Pancreas Article

More on the Artificial Pancreas

For hospitalized patients, diabetics, and those with chronic pain this isn’t a moot point. The question of infusion pump safety can quite literally be a question of life or death.

infusion pump FDA

What Approach: Recommendations or Requirements?

Is this the best approach? Will an infusion pump manufacturer need to follow this recommendation? Or will it lead to confusion on what is actually required and allow inadequate descriptions of the infusion pumps in a medical device 510(k) application. The 510(k) application does not carry the same extensive requirements as an investigational device exemption (IDE) application.

There are a number of things that can go wrong with infusion pumps. Many are controlled with software. FDA issued these comments about potential software problems:

“Unfortunately, in some cases, the software does “go wrong” and compromises patient safety. Because software is inevitably complex, abstract, and intangible, design errors can be difficult to detect. Users and patients should expect infusion pump software to be free from errors. The occurrence of a software error should be a highly unusual event.”

FDA attention infusion pumps

Should Reviewing & Writing New Regulations be an FDA Priority?

I am glad that FDA is giving attention to the issue of infusion pumps. There is a good deal of information besides the draft guidance document that will benefit consumers who need to pay attention to infusion pumps. Again, I notice that FDA begins a major consumer protection initiative on a Friday, when it will receive the least attention. They did the same thing in announcing issues with Simvastatin (see previous post). FDA has also decided to take on this issue with a guidance document, not a regulation. Many of FDA’s regulations are antiquated and in serious need of updating. What to do about software and computer validation is certainly one of the issues that FDA needs to take on.

Part 11- Electronic Records; Electronic Signatures, has been in limbo since 2003. Part 312, the investigational new drug (IND) regulations haven’t had a major review since the 1980s. And the medical device regulations in Part 812 and 814 have received substantial public criticism.

Public health initiatives are a very good thing. Sometimes, however, you need a regulation that can be enforced.

Here is a link to the Infusion Pump Initiative

UPDATE: Here is a link to Compliance Zen that has an excellent post by John Avellanet on “Regulation by Guidance” that discusss this issue. Compliance Zen was recently selected as one of the top 50 blogs for biotech students (see Blogroll).

The New York Times has an extensive article on the topic

Here is the article from Medpage Today


UPDATE: You can now “Like” the Blog on Facebook. They no longer have fans, which I think is an improvement:

GxP Perspectives LinkedIn Group

FDA Warns Pfizer After Children Receive Overdoses in Clinical Trial

April 20, 2010

FDA Pfizer Warning Letter

FDA Warns Pfizer

FDA took on the largest pharmaceutical company in the world, Pfizer, after FDA documented that as many as 13 children were overdosed with the drug Geodon, being studied to treat bipolar disorder. In a one month inspection an FDA field investigator, accompanied by a physician from the Center for Drugs, Division of Scientific Investigations (DSI), reviewed Pfizer’s conduct. It took FDA 11 months to write the Warning Letter, dated April 13, a delay that would not have been permitted a few years ago. However, in the past three years FDA has cited three of the largest pharmaceutical companies for failures as a sponsor of clinical trials.

All three were cited for the failure to monitor the progress of the investigation, an activity that is more likely than not contracted out to CROs- Contract Research Organizations. The other two large sponsors, Sanofi-Aventis and Johnson & Johnson, used CROs to monitor their studies. It is not clear from the Warning Letter if Pfizer used a CRO for the audited studies. There were other dosing errors of concern to FDA in the Warning Letter. Pfizer was also cited for informed consent issues and failure to have cardiologists available to read safety ECGs.

FDA had this to say about Pfizer’s conduct on monitoring:

FDA regulations require that sponsors ensure proper monitoring of clinical investigations. Our investigation found that Pfizer failed to properly ensure monitoring of the study referenced above. As a result of inadequate monitoring, widespread overdosing of study subjects at multiple study sites was neither detected nor corrected in timely manner.”

Pfizer responded to FDA as reported by the Associated Press, in an article by Matthew Perrone.

Pfizer Warning Letter

Pfizer Responds

Pfizer spokeswoman Kristen Neese said many of the problems cited by the FDA were first pointed out by the company itself more than four years ago.

‘Pfizer has communicated with the FDA about our conduct of clinical trials and, over the next two weeks, will provide an outline of new and existing processes for preventing similar issues with Pfizer clinical trials,’ Neese said in a statement.”

It is important to note that FDA had cited Pfizer in the past regarding the failure to monitor clinical trials. Repeat violations are more likely to result in an enforcement action. However, all three of these sponsor Warning Letters indicate that if something goes wrong at a clinical site, such as overdosing children, then the sponsor will be held responsible.

In Pfizer’s defense, it should be noted that Pfizer is the organization that caught the overdosing. The Warning Letter cites Pfizer for not determining that the subjects received incorrect dosages of study drug through their monitoring of the site. However, Pfizer data managers determined the overdose occurred. It seems that Pfizer may have been “monitoring the progress of the investigation” in more than one way, through monitoring visits AND through review of the data by their data management department. It seems harsh to me to cite a sponsor for violations that the sponsor found themselves. Something to think about.

This is the first Warning Letter that Pfizer has received for clinical or other research. They have received Warning Letters in the past for labeling or promotional claims, most recently in 2008.

Read the Warning Letter here:


GxP Perspectives LinkedIn Group

FDA Guidance- Converting Paper Files to Electronic

April 17, 2010

converting paper to electronic FDA guidance

Need to Convert Paper Files?

Converting paper files to electronic records is a practice allowed by FDA and other regulatory agencies. This question is frequently asked by those responsible for maintaining records and the Trial Master File (TMF). Workers who are trying to cut down on the massive amount of storage space needed to comply with FDA record retention policies, an important issue for GCP compliance. However, not only is it allowable, FDA actually tells you how to do it in relatively understandable English. The key guidance document you will need as a reference is:

Guidance for Industry: Part 11; Electronic Records; Electronic Signatures- Scope and Application (August 2003).”

Here is what the agency has to say:

4. Copies of Records

The Agency intends to exercise enforcement discretion with regard to specific part 11 requirements for generating copies of records (§ 11.10 (b) and any corresponding requirement in §11.30). You should provide an investigator with reasonable and useful access to records during an inspection. All records held by you are subject to inspection in accordance with predicate rules (e.g., §§ 211.180(c), (d), and 108.35(c)(3)(ii)). We recommend that you supply copies of electronic records by:

• Producing copies of records held in common portable formats when records are maintained in these formats

• Using established automated conversion or export methods, where available, to make copies in a more common format (examples of such formats include, but are not limited to, PDF, XML, or SGML)

In each case, we recommend that the copying process used produces copies that preserve the content and meaning of the record. If you have the ability to search, sort, or trend part 11 records, copies given to the Agency should provide the same capability if it is reasonable and technically feasible. You should allow inspection, review, and copying of records in a human readable form at your site using your hardware and following your established procedures and techniques for accessing records.”

I was able to get this information from FDA’s excellent resource, “GCP Questions.” There is a link under FDA Stuff, scroll down beneath the Blogroll on the right, as: FDA Answers to GCP Inquiries. That’s also where you will find the Scope and Application for Part 11 link to the FDA Guidance Document.

I would make a very strong recommendation that before you start converting paper files to electronic ones that you develop a standard operating procedure (SOP) for how you are going to do it. Your files are your story of how a clinical trial was conducted. You want to convert files the right way each and every time.

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], 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.”

FDA Guidance on converting paper files to electronic

Do You Have a Topic for the Blog?

I was asked this question by one of the fine people who has become a Fan of the Blog. You can do so as well. Now Facebook gives you the option to “LIKE” the Blog instead of becoming a “Fan.” I think it makes sense. Anyway, visit the site on Facebook, it is a great way to ask a question or keep up with my experiences with volcanoes. By the way, I just had a trip to Europe cancelled because of some volcano. Oh well.

So I welcome your comments and suggestions. In fact, you don’t have to be a Fan to comment. You can do it by clicking on “Leave a Comment” just below!


GxP Perspectives LinkedIn Group

Clinical Trial Protocol Deviations & Violations- Part II

April 12, 2010

GCP protocol deviation and violations in clinical trials

The Dilemma of Protocol Deviations in Clinical Trials

Protocol deviations or violations are the most common FDA 483 citations by FDA during clinical trial inspections. Recently the Blog featured a guest commentary on Keeping Protocol Violations in Check, in a Guest Commentary by Judith Lynn. Now we have another GxP Perspective by Sarah Wilson, a GCP auditor I have had the chance to work with on several audits over the past few years. Sarah discusses the pitfalls when protocol deviations or violations become practice during a study. She also explains the difference between a “deviation” and a “violation.” I am putting a link to Judith’s commentary at the end of the post so you can compare GxP Perspectives between two excellent professionals.

And now, here’s Sarah:

When Protocol Deviations Become Practice During Clinical Trials
by Sarah Wilson, BS, MS, CCRP

The Food and Drug Administration and the International Conference on Harmonization (ICH) do not distinguish between “deviations” and “violations”. If you take a quick look at the FDA Inspectional Manual, the term “Protocol Deviation” is defined as “A protocol deviation/violation that is generally an unplanned excursion from the protocol that is not implemented or intended as a systematic change” The keywords in the definition should be “not implemented or intended as a systematic change”. Therefore, in this article, protocol deviation and protocol violation are synonymous.

When a clinical investigator agrees to conduct a clinical study under GCPs; he or she typically signs an agreement such as Form FDA-1572. By signing this agreement, the investigator commits to conducting the study in accordance with the approved protocol and that changes to that protocol will only be made as precedence to protect the safety, rights, or welfare of the subject (Title 21 CFR 312.53). Likewise, when the investigator agrees to conduct the study using International Conference on Harmonization (ICH) Guidelines, he or she agrees to “conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authority(ies) and which was given approval/favorable opinion by the ethics committee” (ICH E6, Section 4.5.1).

clinical trial violation GCP

All Clinical Trials Will Have Deviations from the Protocol

Very seldom, if ever, will you find a clinical study without deviations. Subjects do not always return for visits during the protocol allotted time and doctors do not always enroll eligible subjects or perform all of the tests required by the approved protocol. These are all deviations from the protocol and the objective should be to ensure the deviation is not routinely repeated. When deviations occur on a routine basis, it becomes a rule – not an exception and is therefore no longer just a deviation but a “practice”.

Good Clinical Practices dictate that protocol deviations be thoroughly documented, explained and reported to the sponsor. To simply document that the deviation occurred is not enough. When possible, researchers should also document what will be done to prevent reoccurrence, a type of corrective action plan. For example, if site personnel forgot to schedule a subject’s follow-up visit or to order the investigational product in time to dispense to the subject; there should be processes implemented to prevent this from becoming a routine protocol deviation.

protocol clinical trial violation

Good Clinical Practice

Serious deviations/violations, such as failure to follow-up with a subject or an adverse event may also require a report be sent to the approving Institutional Review board (IRB). Many IRB’s tell clinical sites not to send them protocol deviations unless they affect the welfare or rights of the subjects. Documentation showing protocol deviations were reported to the sponsor and IRB (if required) should be available at the site.

Protocol deviations may also occur due to poor protocol development. A sponsor may piggy-back off another protocol and fail to remove components that was important to that particular clinical trial investigation and yet, do not apply to the current investigational therapy. In this case, the author suggests a protocol amendment is the correct course of action, however, many will not submit an amendment. Is there another acceptable means of handling this error that will undoubtedly end up as a protocol deviation?

Test Your Knowledge. Using the Case studies below, decide how you would handle the different scenarios.

Case Study 1
For a psychological study investigating a treatment for bipolar disorder, the protocol requires Dr. X to perform a physical examination that includes a rectal and genitourinary exam. These exams are not typically performed by Dr. X and he therefore, did not do the exams. Dr. X has enrolled 125 subjects and the rectal and genitourinary exam was omitted for each. Is this a protocol deviation and should it be reported to the sponsor? The IRB?

protocol violations clinical trials

Two Case Studies

The example presented in the above case study clearly demonstrates a repetitive protocol deviation. This is no longer a protocol deviation but practice. A conscience decision has been made to omit this part o the physical exam. However, in this particular example, it would not be sensible to issue an amendment to the protocol to omit the exams only because the investigator repeatedly fails to perform them. The sponsor should not use boiler-plate physical exam criteria but ensure the physical exam requested is typical for the specialty under investigation. If such an error occurs, the sponsor should consider issuing a formal document excusing the examination and IRB approval or acknowledgement should be obtained.

Case Study 2
The criteria in many protocols specify acceptable ranges for certain laboratory tests. Let us assume that for this Case Study, Inclusion Criteria require the subjects’ Body Mass Index (BMI) to be 18-35; systolic blood pressure 90-140, diastolic pressure 50-90 mmHg and vital signs taken after 3 minutes rest in supine position. The clinical investigator enrolled 8 out of 11 subjects with a BMI of 36. The clinical investigator felt the number was close enough to the target range that the subjects could be enrolled. Did these protocol deviations become practice?

clinical trial protocol violation FDA

Repeated Protocol Deviations

It would not be uncommon for the investigator to overlook the 1unit difference in the target value and enroll the subjects. However, if the Investigator enrolled several subjects outside the approved inclusion criteria, then this has now become a practice and the sponsor should consider bringing the investigator into compliance or amending the protocol to allow “investigators discretion of clinical significance”. It’s possible that the investigator knows enough about the subjects to know that they will suffer no harm by participating in the study, however, in addition to patient safety, ranges are also often created for statistical evaluations. It is imperative that sponsors and study monitors ensure data is obtained based on approved criteria for subject safety and data integrity.

In conclusion,
we accept that protocol deviations inevitably occur in nearly any given clinical trial. This means the action taken was inconsistent with the Food and Drug Administration (FDA) and Institutional Review Board (IRB) approved protocol. Sponsor and clinicians should remember that deviating from or violating a clinical trial protocol presents many opportunities for failure. Consistent deviations, in my opinion, are a blatant disregard for Good Clinical Practices (GCP) and can potentially affect the rights and safety of the subjects participating in the clinical trial. It can also jeopardize the quality and reproducibility of the research data. Routine deviations from an approved clinical trial protocol are unacceptable and mandates an amendment to that protocol or investigational plan because routine protocol deviations are no longer just a protocol deviation – it is practice.

Thanks Sarah! Check out Sarah’s Blog, “QA Talk” on the Blogroll and right here:


You can help out GxP Perspectives! Please let your colleagues and friends know about GxP Perspectives. I also encourage you to get an email subscription (on the sidebar to your right) or join the LinkedIn group (below).

SPECIAL UPDATE: 18MAR2011: FDA has released an updated version of the Compliance Program Guidance Manual 7348.810, Sponsors/Contract Research Organizations/Monitors. There are new sections on registration of clinical trials on, Financial Disclosure, the Part 11 Scope & Application Guidance Document, and other issues. If you work for a sponsor, a CRO, or are a contract CRA you MUST read this document. Review Section III, Inspectional.

A new feature from FDAzilla on FDA 483s

Read the Press Release on 483s



Protocol Violations: Root Cause Analysis

GxP Perspectives LinkedIn Group

You can also read what Judith Lynn has to say on the subject:

FDA Warning Letter to Oncologist Raises GCP Questions

April 8, 2010

FDA Warning oncologist

Incorrect Calculations Resulted in Overdose of Subject

FDA issued a Warning Letter to a California oncologist that raised some questions about basic adherence to GCPs, not only by the oncologist, but also the sponsor and/or CRO. The Warning Letter, dated 17 March 2010, cites the Oncologist for the failure to calculate the study drug dose correctly. FDA stated “this miscalculated dose unnecessarily exposed the subject to an overdose, with the potential for increaased adverse events.” Patient endangerment is always a primary concern of FDA. Although only one subject received an overdose and the FDA accepted the PI’s corrective actions, it still resulted in being listed first on the Warning Letter. The most significant finding should be the first item listed on a Warning Letter.

The Warning Letter was issued by the Division of Scientific Investigations (DSI) in the Center for Drug Evaluation & Research. DSI had formerly been the FDA office that issued the fewest Warning Letters for GCP inspections. In 2005 and 2006, according to one report, DSI did not issue a single Warning Letter to clinical sites. In Fiscal Year 2008 there were at least 12. This sharp increase indicates an increased emphasis on enforcement brought on when Dr. Leslie Ball became DSI Director. I am attaching a link below to publicly available slides from a GCP presentation Dr. Ball gave to an industry meeting for her viewpoints on GCP compliance.


oncology GCP FDA

Adequate Resources for Chemotherapy PK Study

Half of the Warning Letter to the oncologist is a detailed listing of pharmacokinetic (PK) samples that were analyzed incorrectly. The listings show that, “Specifically the samples were collected after completion of the infusion rather than after initiation of the infusion.” It is not often that PK samples make their way into a Warning Letter. Perhaps this is a sign of things to come. The Warning Letter notes that study nurses and pharmacists were retrained, a corrective action not accepted by FDA. The question remains on how they were trained at the beginning of the study. It also could lead to questions about staffing levels during the PK portion of the study and if the investigator had allocated adequate resources.

Adverse Events:

GCP oncology Warning Letter

Too Many Queries for eCRFs?

The last citation was the failure to “maintain adequate and accurate case histories” and lists eight adverse events in source documents that had not been entered into the case report forms (CRFs). It turned out that the site had developed a policy to enter data into the CRFs during the sponsor’s monitoring visits to cut down on the number of queries they were receiving. The site was using an eCRF system. FDA noted that it would be 8-15 months from the adverse event being entered onto a progress note to being entered into the eCRFs. FDA stated that this was an unacceptable delay and the delay “may have jeopardized subject safety.” Again, the safety of study subjects triggered FDA concerns.

GxP Perspective:

This Warning Letter raises a number of GCP questions about compliance with FDA regulations. Here are several to start with:

1. Where was the sponsor and/or CRO? It is the responsibility of the sponsor to select sites that have adequate resources. Did the sponsor review the PK samples with staff and ensure that they had been trained and had the resources to complete the study?

2. Where were the monitors? Why were there adverse events going unreported for 15 months? The primary responsibility of a monitor is to perform a comparison of CRFs against the source documents. Were the monitors properly trained? Were they given adequate time to review study charts or was it a case of “rip and run?”

3. Was there a major problem with the eCRF system? I have noticed in the past year or two that a number of eCRF systems are not yet ready for prime time. FDA recently issued a Warning Letter to a clinical site because they did not have access to the eCRFs from the vendor and could not print them out for an FDA field investigator. What were the reasons for the high number of queries? How did the sponsor respond?

GCP FDA oncology

GCP Questions on Responsibilities

Usually when FDA issues a Warning Letter it is perfectly clear where the responsibility lies. However, this time I wonder how much of the problem resides with the sponsor, the CRO and other clinical trial vendors. It will be interesting to see if there are future Warning Letters for sponsor responsibilities. It is quite possible that the clinical site will soon have company.

Here is the Warning Letter:

Here are Dr. Ball’s slides:

Ball-Harmonizing Regulatory Approaches to Clinical Trials


GxP Perspectives LinkedIn Group

Filing Regulatory Submissions to FDA: Ten Tips for Success

April 4, 2010

success FDA regulatory submission

The Long Road to a Successful Regulatory Submission

Quality regulatory submissions to FDA are hard work. A successful NDA or PMA is the result of dedicated teams of people working under stressful conditions. Time-frames can be demanding with anxious investors at one end and the scrutiny of FDA at the other. How do you keep your sanity through it all? Good question. The same formula can be used whether you are working on an IND for a promising candidate or a PMA or NDA for final approval.

We have a Guest Commentary by veteran regulatory consultant Louise Johnson to help provide some clarity.

Guest Commentary:

Ten Things I’ve Learned to Make Regulatory Submissions Effective and Maintain My Sanity At the Same Time

1. Write the Table of Contents (TOC) first. While you may already have a detailed project plan, there is no better way to ensure your submission is complete than to write a detailed TOC. This should be sufficiently detailed to include each individual document.

2. Know the purpose of each document. I once received a draft pharmacokinetic (PK) study report that did not include the PK data! Obviously, this document did not meet its purpose and is an extreme example. Keep in mind that each document makes a unique contribution to the submission. When a document is written without an understanding of its role, the submission may be incomplete and could result in more questions from reviewers.

3. Create submission timelines with the entire team in person.

submission regulatory approval FDA

Set Timelines

Discussion of detailed timelines allows team members to explain their timing needs and the impact of other team members’ activities on their work. Allowing team members to have input into timelines increases their commitment to reach their goals and to support others reach their goals. If the team finds there is a risk of not meeting corporate goals, that information can be communicated upward to discuss alternative approaches (identifying additional resources, refinement of the goal, etc.). I’ve been on teams that had impossible timelines assigned to them by upper management – nothing kills morale faster than believing you have been put in a position to fail.

4. Define what final means – there is no such thing as a final draft. Believe it or not, final can mean very different things to different people. Some authors think that drafting a document makes it final since they’ve done their part. A regulatory person defines final as a complete, approved document that is ready to be inserted into the submission. Since a fair amount of time can transpire between a draft document and the approved version, make sure the team has a common understanding of when a document is final.

5. Limit the number of draft versions of a document.

FDA success regulatory submission

Limit Your Edits

It can be tempting to add just one more piece of information after a document has been circulated for review. Do not do it! You run the risk of reviewers commenting on different versions, which confuses everyone and increases the chance of errors. Reviewers have limited time and the quality of their review decreases the more times they’ve seen the same document with only minor tweaks between versions. It’s also much more difficult to track 6 drafts than 2 drafts. Spend the time to make each draft as complete and accurate as possible and you will spare yourself the misery of trying to keep track of different sets of comments and different draft documents.

6. Know when to stop editing a document. When a document meets its purpose in the submission, is correct, and is easy to understand, it is complete. When comments or switch back and forth between alternate ways of saying the same thing or are predominantly changes to writing style, you are no longer adding quality to the document.

7. Do it right the first time. In the long run, shortcuts will cost more time than they save. Even something as simple as running a spell check before distributing a document for review makes a big difference. Do you really want highly trained scientists spending their time correcting spelling errors? In extreme cases, a clinical study may need to be repeated if adequate time and thought was not put into the study design. For some small companies, the failure of a clinical study has meant the failure of the company. In most cases, though, you can reduce the number of review cycles for documents, avoid duplication of small studies, and decrease costs if you invest appropriate time at the beginning.

8. Identify team member absences ahead of time. I’ve worked on submissions where a critical team member was needed for a last-minute approval and no one could get in touch with him. We were able to get approval from another manager, but it required time and energy to identify that backup person. Any absences are critical close to the filing date, when the team is scrambling to finish the submission. If you have identified team members who will be absent and have identified their backups at the beginning, you’ll be able to efficiently complete the submission without wasting time and energy looking for people.

9. Know when to take a break.

FDA regulatory submission success

Take Time to Relax

It can be tempting to think that the more you work, the better the submission will be. However, as you tire, your ability to think strategically and creatively decreases. I’ve found I often come up with a solution to a problem after a good night’s sleep. I’ve also quickly found errors from the previous day by getting sufficient rest. In my worst experience, we submitted a briefing package for an Advisory Committee meeting that included a discrepancy in the number of people who died during the clinical development program. The next morning, the error practically leapt off the page at me. While it was easy to correct the error, I would have much preferred to delay the submission by a day and submit an accurate document.

10. Keep a sense of humor.

regulatory submissions FDA

Remember to Have Some Fun

Important submissions can be stressful and it’s possible to see people behaving in less than ideal ways. If you can keep your focus on the big picture and see humor in everyday challenges, you can actually enjoy working closely with the team and develop trust and respect for each other. I worked on one submission that was very important to corporate headquarters; we were asked to provide daily updates. This seemed burdensome because we were so busy, but we decided to send photos of different people working on the submission each day. This made the updates fun for us. Headquarters loved the photos and developed a better understanding of the challenges we faced.

By Louise Johnson

There is more Guest Commentary at the page at the top of the Blog. Read about protocol deviations, CAPA Basics, and informed consent.


The blog, FDA Matters has another interesting post, I now subscribe to weekly updates, on 12 years of exclusivity. He says he “asked Congressional staffers: how many of the Senators and Representatives understand that the follow-on biologics debate is about the amount of data exclusivity, not market exclusivity?”

I certainly didn’t know. Check it out:

GxP Perspectives LinkedIn Group

%d bloggers like this: