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FDA Guidance Documents Released Recently

Article reviews FDA guidance documents released in the past few months including the new Final FDA guidance on biocompatibility released June 16.

ODE Final Guidance Documents FDA Guidance Documents Released Recently

For anyone that is responsible for monitoring new and revised regulatory requirements, the FDA guidance documents are something you probably check at least once every month. If you are not familiar with these FDA resources, here are the links for two of the medical device FDA guidance documents webpages:

New Final FDA Guidance Documents

The last time I reviewed an FDA guidance document was in February for the new guidance document from the FDA related to usability engineering and human factors engineering. There was a new final FDA guidance document released by the office of device evaluation on June 16: “Use of ISO 10993-1“.This biocompatibility guidance was expected for release in December, but the release was delayed.

Use of ISO 10993-1

The new biocompatibility guidance that was published last month provides specific guidance about the application of certain tests required for demonstrating biocompatibility. For example, test article preparation and risk assessments for the applicability of specific tests is addressed. A revised test matrix is included in the guidance document. Special considerations are provided for each of the following biocompatiblity tests:

  • cytotoxicity,
  • sensitization,
  • hemocompatibility,
  • pyrogenicity,
  • implantation,
  • genotoxicity,
  • carcinogenicity,
  • reproductive and developmental toxicity, and
  • degradation assessments

New Final Rule for Symbology

In addition to FDA guidance documents, the FDA also released a final rule on symbology that will modify 21 CFR Parts 600, 801 and 809. The FDA is finally changing its position on acceptance of harmonized symbols in lieu of English text. The FDA is accepting ISO 15223-1 as a recognized standard and allowing manufacturers to use the symbols instead of English text in order to facilitate global harmonization of labeling. The FDA is only allowing the use of Rx-Only as to indicate that a product is prescription only. The guidance even defines the acceptable process for creating new product-specific pictograms. The effective date of the new final rule will be September 13, 2016. 

New Draft FDA Guidance Documents

In addition to final FDA guidance documents, there have been several new draft guidance documents that were released recently:

  1. List of Highest Priority Devices for Human Factors Review
  2. Public Notification of Emerging Postmarket Medical Device Signals (“Emerging Signals”)
  3. Characterization of UHMWPE for Orthopedic Devices
  4. Technical Considerations for Devices for Additive Manufacturing

The second two FDA guidance documents focus on materials that are important for orthopedic manufacturers, because UHMWPE is used as a wear surface for join implants and many of the implants and instruments are now being manufactured using additive manufacturing instead of forging, casting or milling bar stock.

How to keep up on FDA Regulation Changes

If you are interested in keeping up on new and revised regulations from the FDA, I wrote a blog explaining 4 ways to to identify new and updated FDA regulations. The blog identifies FDA webpages for the following 4 types of updates:

  1. Guidance Documents
  2. Recognized Consensus Standards
  3. Device Classifications
  4. Total Product Lifecycle (TPLC) Database

The ISO 15223-1 standard for medical device symbols has been released for several years, but it was not recognized by the FDA until June 14, 2016. The recognition of the Standard is part of the implementation process for the new final rule regarding the use of symbology for medical device labeling. The timing of this new final rule coincides with implementation of UDI labeling requirements for Class II devices. In addition, the new European Medical Device Regulations now specify labeling requirements for the primary sterile packaging as part of Essential Requirement (ER) 19.2:

  • (a) an indication permitting the sterile packaging to be recognized as such,
  • (b) a declaration that the device is in a sterile condition,
  • (c) the method of sterilization,
  • (d) the name and address  of the manufacturer,
  • (e) a description of the device,
  • (f) if the device is intended for clinical investigations, the words: ‘exclusively for clinical investigations’,
  • (g) if the device is custom-made, the words ‘custom-made device’,
  • (h) the month and year of manufacture,
  • (i) an indication of the time limit for using or implanting the device safely,
  • (j) an instruction to check the Instructions For Use for what to do if the sterile packaging is damaged etc.

These new requirements will require many manufacturers to redesign labeling for sterile packaging and the ability to use symbology will assist in creating globally harmonized labeling.

Posted in: FDA

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FDA 483 Inspection Observations Pareto Chart for FY 2015 Data

This article presents a Pareto Analysis of FDA 483 inspection observations from FY 2015 and compares the trends observed with a similar Pareto analysis that was performed a couple of years ago on FY 2013 data.

FY 2015 Pareto Analysis of FDA 483s FDA 483 Inspection Observations Pareto Chart for FY 2015 Data

Method of Data Analysis for FDA 483 Inspection Observations

The FDA posts Excel spreadsheets on it’s website in order to download data for FDA 483 Inspection Observations. These spreadsheets include inspection results for all the divisions of the FDA. In order to perform a data analysis for FY 2015 results, I deleted the sheets that were not specific to medical device manufacturer inspections (i.e., only used data from CDRH). I sorted the data by the regulation that was referenced. For example, all the sub-clauses for 21 CFR 803 were combined into one category for the Pareto analysis. The combined categories were then sorted from the most frequent 483 inspection observation to the least frequent 483 inspection observation. The data was then added to the graph that I produced in February 2014 using FY 2013 results as a second data set. The resulting graph is shown above.

Comparison of FDA 483 Inspection Observations between FY 2013 and FY 2015

For MDR Compliance (i.e., 21 CFR 803), there was a slight increase in the number of 483 observations issued from FY 2013 to FY 2015. However, the difference was only a 1% increase from 6.2% to 7.2% of the total number of 483s issued. There was an even smaller increase in the number of findings related to purchasing controls (i.e., 5.6% increased to 6.1%). I noticed a slight drop in the number of findings related to design controls, CAPA and complaint handling. However, the overall trend for FY 2013 and FY 2015 is essentially the same.

There are two other categories where an increase was observed: 1) process validation increased by 0.7% from 4.8% to 5.5%; and 2) control of nonconforming product increased 0.8% from 4.3% to 5.1%. These areas are important. Control of nonconforming product is one of the major sources of CAPAs and often results in design changes. Therefore, FDA inspectors are reviewing your data for nonconforming product during inspections  in order to help them identify potential CAPAs and design changes that may have been made. The typical sequence is: 1) nonconformity, 2) investigate nonconformity as part of a CAPA, and 3) initiate a design change as a corrective action.

Process validation is a completely different area that is separate from CAPA, complaint handling and MDRs. However, inadequate process validation is a common root cause for nonconformities. Therefore, inspectors often follow an audit trail from a nonconforming product record back to a process change that was implemented but inadequately validated. Therefore, an increased focus on nonconformities may be the reason for an increase in FDA 483 inspection observations related to process validation.

So what’s the big deal?

This proves that the FDA inspectors continue to be predictable. The “playbook” for FDA inspections is the QSIT Manual. It hasn’t changed since 1996. Yet, companies continue to be shocked and amazed by FDA inspectors.

Additional Resources

If you want to learn how to prepare for FDA inspections, I recorded a webinar you can download (FREE). I recorded the webinar in May of 2014, but it’s been a couple of years and I’ve learned a few new tricks. Therefore, I’m going to re-record the webinar and update it for lessons learned. I’ll even share a few tools and approaches to avoid findings and reduce the risk of warning letters. I’m even evaluating a new application that is designed for teams to have private chats and file sharing during an inspection. Stay tuned to my webinars page and I’ll post that webinar soon. Maybe I’ll record something from Germany next month.

Until then, I am working on an webinar specific to medical device reporting. Many companies have still not updated their MDR procedures to reflect the eMDR process using electronic submissions gateways. Therefore, I’m releasing an updated procedure for MDRs and I am offering a webinar bundle to train people how to comply with 21 CFR 803 and the procedure. You might also be interested in my previous webinar specific to control of nonconforming product.

Posted in: FDA

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Finally, New European Medical Device Regulations are Confirmed!

This article announces confirmation of the New European Medical Device Regulations by negotiators of the Dutch presidency of the Council and EU Parliament.

Confirmed Finally, New European Medical Device Regulations are Confirmed!

Announcement of New European Medical Device Regulations

Yesterday, May 25, the European Parliament and the Dutch presidency of the Council reached an agreement and it was announced in press release.

The agreement is subject to confirmation by permanent members of the Council and Parliament’s Envi Committee. The new regulations include the following substantial changes:

  • A scrutiny process for high risk (i.e., Class IIb implants and Class III) products
  • Eudamed database will be expanded to provide public access to information about Notified Bodies, Economic Operators (i.e. – manufacturers, importers, distributors, authorized representatives, etc.) and comprehensive product information
  • Eudamed database will become publicly accessible for searching market surveillance and vigilance data (similar to the FDA’s MAUDE database)
  • Implementation of a Unique Device Identifier (UDI) requirement in Europe.

The Eudamed database will be an invaluable global resource for manufacturers, physician and patients.

Next Steps for New European Medical Device Regulations

The next step in the process of approving the new regulations is an invitation of the Council’s Permanent Representatives Committee and the Parliament’s ENVI Committee to endorse the agreement. The regulations will finally be adopted by the Council and the Parliament after Committee approvals and we can expect implementation of the regulations this fall. The new regulations will have a three year transition after publication for medical devices and a five year  transition for in vitro diagnostic medical devices.

MedTech Summit June 13-17

On June 13 I will be in Brussels at the MedTech Summit hosted by Informa Life Science. There will be 300+ attendees with a fantastic assembly of industry experts representing the Competent Authorities, Notified Bodies and manufacturers. This meeting provides a unique opportunity to learn and discuss the details of the New European Medical Device Regulations and the challenges we will all face in the preparation for the transition to the New European Medical Device Regulations. I will have the pleasure of speaking about risk management and its integration with device design, post-market surveillance and labeling. I will also be Chairperson for the Labeling Stream in June 16.

Please stay tuned to my blog feed. I will be posting related blogs over the next month.

Register for the MedTech Summit

Click on the blue text above to register or you can also call Informa Life Sciences at: +44 (0) 20 7017 7481 or registrations@informa-ls.com.

New Live Webinar on MDRs June 9, 2016

I’m releasing an updated procedure for MDRs and I am offering webinar bundle to train people how to comply with 21 CFR 803 and the procedure. The webinar is scheduled for June 9. I’m even offering two times to accommodate companies in Europe as well as the USA.

Here’s a link for the webinars page.

Posted in: CE Marking

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Time management to prevent work overload: Top 10 ideas

This article lists my top 10 ideas for time management to help prevent work overload–including suggestions for apps and other resources.

Handling Work Overload 1 Time management to prevent work overload: Top 10 ideas

I am a workaholic and I don’t recommend it–unless overweight, out of shape, friendless and divorce sounds like a great life plan. I work with regulatory affairs and quality assurance managers at every client, and 100% of them have insufficient resources. Expectations internally and externally never decrease. The saying used to be, “Do more with less.” Now it feels like we have one egg, one basket and we are expected to save the world.

Stop feeling sorry for yourself. Every department manager feels this pressure. If you don’t believe me, look around you. Everyone is popping 400mg of ibuprofen and stressed to their limit.

So what can you do to make things better?

That question is critical. It shows that internally you acknowledge that you can do something to make things better. I obviously don’t have all the answers, but I have found some tools in the past year that really made a magnificent difference in helping me with time management. 100% of these ideas were suggested by others that appear to be more at peace and happier than I was last year.

#1 Get some sleep

Two years ago I woke up after 3-4 hours of sleep every night. Last year I was almost up to 6 hours of sleep on a good night. Now I am consistently getting 6-8 hours of sleep, and once I slept for 9 hours. There are lots of suggestions for how to get more sleep, and I’ve tried them all. What works for me is: 1) no alcohol or coffee within 4 hours of bedtime, 2) melatonin just before bed, 3) exercise every day, 4) eating well, and 5) a habit of reading each night to calm myself and relax. I also use a white noise app on my phone.

#2 Budget your time management

You will never get everything done. It’s a fact. Just like money, you can always spend more. Instead, decide how much of your life you want to spend doing things. Don’t micromanage your time. Think of the big picture. There are 168 hours in a week, and >42 hours should be spent sleeping. 40-50 hours a week will be spent working. 5-10 hours per week will be spent getting to work. More than two-thirds of your life is spent sleeping and work-related–if you’re not a workaholic. Be very selfish of how you budget the remaining third of your life. I like to re-read habit #3 from Steven Covey’s book “7-Habits of Highly Effective People.” It will help you remember what’s important. Your priorities should be physical health, mental health and your family. If you devote an hour a day to each of those, you might have time left for eating, grooming and reading a book. Yes, you need vacations too!

#3 Minimize multitasking

Some people believe time management is managing multiple tasks at once, but it is actually less efficient to multitask. Picking something up, putting it down, picking it up again…didn’t you learn from your lean manufacturing training that motion, waiting and queue are all muda (i.e., waste). You need to start a task, finish that task and then start the next task. If you want more advice on this topic, try reading “Getting things done” by David Allen. This one was recommended to me by an uber-productive orthopaedic surgeon.

#4 Don’t forget to “sharpen the saw”

This is the seventh habit from Covey’s book. You should never stop improving. For example, entrepreneurs need to learn marketing. I don’t have time for an executive MBA to learn marketing. Instead, I teach myself every day while I’m working out. I have a bicycle on a trainer set-up in front of my TV. The TV is only connected to the internet. If I need a break, I watch Netflix while cycling. However, usually I’m listening to podcasts, watching YouTube videos about marketing and software tools or I’m reading books on my Kindle. I also purchase a lot of audiobooks that I listen to in the car while driving my children to rock climbing, soccer, plays and during my two-hour ride to and from the nearest airport. This is the only kind of multitasking I’m good at.

#5 Just say no.

You need to put first things first (i.e., habit #3). On a scale of 0-10, how important is it. Is it important to you, your boss, your spouse, your children or your best friend. If not, why are you wasting your precious time on it. Say no. If it’s a 9 or 10 to your spouse, say yes–even if it’s a 2 on your scale. If you have a time conflict with two items that are high on the scale, then you need to find a win-win (i.e., habit #4). This is why communication skills and empathic listening (i.e., habit #5) are the most important skills you will ever learn.

#6 Don’t read your emails “real-time”

You should have a plan for what you are going to do each day. Reading your emails throughout the day will result in reactive behavior that will always result in time management failure. Be proactive (i.e., habit #1). Read your emails just before lunch in a batch and just before you go home in a batch. You should also read “Getting things done” by David Allen. He has fantastic advice for how to process emails. This is an area I’m still working on, but I get 400+ emails a day and that doesn’t include spam, social media or promotions. You should also tell people you work with, “Call me or text me if it’s important.” Good advice for any client of mine. For example, you should probably text me if the FDA is coming on Monday and you need my help.

#7 Use productivity apps for time management

Microsoft seems to have a strangle hold on corporate America, but Outlook is a horrible tool for managing your tasks and time. You need something for personal time and personal tasks, because you have less time available for the things that are more important in your life (i.e., health, family and friends). If I empty the milk carton, I grab my phone and add milk to my “Out of Milk” app. I also use this app for planning what I need for trips, meetings and Christmas present ideas for the kids. Evernote is an uber-app. It organizes everything. Website links, blog ideas, business cards, photos, an address, directions, photos of the person I’m meeting and I use it for lists too (if I already have it open instead of Out of Milk). If you want to know how the most productive people in the world use apps like Evernote, John Lee Dumas includes apps like Evernote in every entrepreneur interview he does–1,303 podcasts and counting.

#8 Block off time to get work done

Some people believe that time management only involves scheduling meetings. You schedule weekly meetings with your boss. You schedule lunch meetings. You should also block off some time for getting work done–without interruptions. You might try blocking off every day from 11:30-Noon for emails, Noon-1pm for a lunch and a walk and 4:30-5pm for emails. If you need to review complaints each day for the need to report as an adverse event, block off some time for that each day. My advice would be to devote time to reviewing CAPAs, complaints and MDRs every day. These are the most critical areas for FDA inspections and you can’t afford to let these tasks fall behind. If you have these tasks assigned to you, then you work on the most urgent task and get it done. Then you schedule the next step for that CAPA, complaint or MDR and go onto the next task you scheduled. If you manage these processes, then you should block off time for reviewing metrics and investigate the exceptions. If it seems like you never have enough time in your schedule for all the tasks, maybe you need to delegate some of those tasks to other departments or people in your department.

#9 Schedule shorter meetings

Not all meetings deserve 1 hour. Some things can be done in 15 minutes, 30 minutes or 45 minutes. Learn about good meeting etiquette, make an agenda and manage the meeting so it’s done on-time or early. Make sure you show up on-time and get it done on-time or early. If people leading meetings are poor at time management, do not let them lead the meeting.

#10 Schedule breaks too

Outlook will allow you to schedule back-to-back meetings from 7am to 7pm (or longer). That doesn’t mean that you should, and that is definitely not good time management. Time management needs to create windows of time where you can rest too. I drive a lot. In order to survive 50,000 miles of driving a year with a congenital spine defect (i.e., L5 fused to pelvis one one side), I need to take breaks and stretch. When I don’t do this I pay dearly. The same thing happens to me when I try to work 12 hours straight without a break. You will be more focused and productive if you take a break once and while.

Posted in: Education

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Special Controls Guidance Document – Content and Format

This article explains the content and format of a special controls guidance document issued for Class 2 medical devices regulated by the CDRH division of the US FDA.

Searching Guidance Documents Special Controls Guidance Document   Content and Format

There are many differences between Class 1 and Class 2 medical devices regulated by the FDA, but one of the primary differences is that many (not all) Class 2 medical devices have a special controls guidance document. Class 1 devices only have “general controls.” These “special” guidance documents can be found on the FDA website by searching the guidance document database. The title of each guidance document typically begins with “Class II Special Controls Guidance Document.” The middle of each title specifies the device type, and the end of the title states, “- Guidance for Industry and FDA Staff.” However, there are many exceptions.

Status of a Special Controls Guidance Document

A guidance document may be a final guidance or a draft guidance. Only the final guidance is considered official, however, draft guidance often indicate what the FDAs current thinking is on a topic. Draft guidance documents sometimes take years before they are approved as a final guidance. Sometimes the draft is so controversial that it will even be withdrawn. The FDA also publishes a list each year of planned guidance documents for the next fiscal year. Some of the final versions of special controls guidance documents were written in the 1990’s, but these documents remain the current final guidance until a new final guidance is approved. Often there is no urgent need to update a guidance document, because there are one or more active ISO Standards specific to the product classification and the standard(s) is recognized by the FDA.

Outline of a Recent Special Controls Guidance Document

Here is the general outline that is currently being used by the FDA for a special control guidance document for Class 2 devices:

  1. Introduction
  2. Topic – Background
  3. Pre-Market Notification – Background
  4. Scope
  5. Risks to Health
  6. Specific Device Description Requirements
  7. Performance Studies
  8. Device Specific Labeling
  9. References

Each product classification has the potential for slightly different requirements due to the differences in types of devices. For example, in vitro diagnostic products do not have animal studies and typically have human clinical study requirements for the performance section of the guidance document. However, an implant is more likely to have details about the materials of construction, biocompatibility and sterilization.

Searching the Guidance Database

There are 8 fields that are searchable for the guidance database.

  1. Product
  2. Date Issued
  3. FDA Organization
  4. Document Type
  5. Subject
  6. Draft or Final
  7. Open for Comment
  8. Comment Closing Date on Draft

For a De Novo application, I sometimes need to create a proposed draft special controls guidance. For this activity, I prefer to find a representative template. In order to do this, I will typically use four of these search fields. First, I narrow the product field to “medical devices” and the FDA organization to “CDRH.” Second, I select “guidance documents” for the document type. Finally, I select “premarket” for the subject and “final.” This narrows the list to 374 documents. Not all of the 374 documents are specific to a product classification, because some of these documents cover more general premarket issues such as risks of wireless telemetry.

You can further narrow your search by adding a word or words to the keyword search field. Therefore, if you are looking for a specific guidance you can find it very quickly.

Format of Special Controls Guidance Documents

If you submit a proposed draft guidance to the FDA (anyone can do this), there is no specific required format. However, I recommend copying the most recent format used by the FDA in order to minimize the amount of work required by the FDA for modifying the guidance prior to publishing your guidance as a draft. You also do not need to include all the sections of a guidance. Some of the guidance documents only update certain sections where technological characteristics have recently changed significantly. Most importantly, if you have a strong reason for deviating from what the FDA has always done–do it. The format of guidance documents has changed since the 90’s and will continue to do so.

Additional Resources

If you are preparing a premarket notification (i.e., 510k submission), you might have more questions than just guidance document availability. You might be interested in purchasing “How to Prepare Your 510k in 100 Days” or the on-line 510k Course or one of our Live 510k Workshops.

Posted in: 510(k)

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Minimum Data Points Constituting a Trend Is 3?

This article explains why three is never the right answer, and this article explains why asking how many minimum data points are needed to identify a trend is the wrong question.

Minimum Data Points for CAPA Minimum Data Points Constituting a Trend Is 3?

Recently a client sent me an email asking the same question about data analysis in two different ways. The first question asked, “How many of the same situation need to occur before it is considered a trend?” The second question asked, “How many nonconformities can occur before a CAPA should be opened?” This question can be asked a hundred different ways, but it’s the wrong question.

Minimum Data Points for Variable Data

In the graph above we have variable data rather than attribute data. When you have variable data, the answer regarding the number of minimum data points is always a quantitative answer that is objective rather than subjective. Typically the new data point lies outside of the upper or lower specification for the element being measured (i.e., >6.6 or <6.1 in the graph above). Even if the new data point remains within specifications, a CAPA may still be issued if the new data indicates that there has been a shift in the normal distribution of data.

In our graph above, on March 13 the newest data point was 6.37. Although this value is within specifications, in fact close to the center of the range, this value represented a shift in the trend that exceeded the normal distribution of data observed for the previous 12 days of the month.  The mean for the first 12 days was 6.54 and the standard deviation was 0.0250. Many people establish alert limits that equal mean +/- 2x standard deviation (i.e., 6.59 and 6.49) and the action limit is often set equal to the mean +/- 3x standard deviation (i.e., 6.62 and 6.47). Therefore, a value of 6.37 is well outside the normal distribution for the first 12 days of the month–but not outside specifications.

The shift in data values for this graph indicates a shift, but the process was capable of remaining within specifications before the shift and process capability actually appears to be slightly better after the shift. In this case, there is no need for a CAPA but if the reason for the shift is unknown an investigation would be recommended. However, if different lower specification were chosen (e.g., 6.4) then the new data point on March 13 would be outside the specification and product would be identified as nonconforming.

Nonconforming results should always trigger in an investigation?

If the process was validated and the mean +/- 2x standard deviations remains within the specifications, then greater than 95% of the product should be conforming. If the the mean +/- 3x standard deviations remains within the specifications, then greater than 99.5% of the product should be conforming. Therefore, based upon the data from the first 12 days of March any data points that are lower than 6.47 should be very rare unless there is a process shift.

An investigation of the data point on March 13 should result in a CAPA unless the outlying data can be explained and a new trend with a lower mean is expected. If the new data point cannot be explained, then only one new data point is needed and the data does not even need to be nonconforming. If no actions are taken the drop in the measured value could continue and nonconforming product could result, while any action taken on March 13 is a preventive action.

Minimum Data Points for Attribute Data

In the case of the first question, the negative customer situation that is reported to a company may be an attribute rather than variable data. For example, “customer unsubscribed” after an email blast went out is a negative customer situation. If you know the % of customers that unsubscribed when email blasts go out, then you have variable data. If you only know that one person unsubscribed, then you only have an attribute (i.e., unsubscribed instead of continued subscription). The first time an unsubscription occurs, you should do an investigation to see if there is an issue other than frequent email blasts that exceed a customer’s expectations in frequency. The action taken could be to establish an alert and action limit for unsubscribed emails based upon industry norms or the % calculated from the first event.

What are the right questions?

Instead of asking how many minimum data points are needed to initiate a CAPA, we should make sure we are measuring the right variables. The % of unsubscribed is a valuable variable data point, but knowing that one person unsubscribed without knowing how many people received that email blast is not nearly as helpful in making future decisions. Another question is to ask, “Why did the person unsubscribe?” If the reason is unknown, you may want to contact the former subscriber and ask them–but probably not by email. If you have a theory why people are unsubscribing you can also perform an experiment to test your hypothesis. If you think the cause is that emails are being sent too frequently, then you can split your list and send the same emails to two halves of a list at different frequencies. If you are correct, then the list that has more frequent emails should also have a higher % of unsubscribers. This type of design of experiment (DOE) is one of the root cause investigation tools I recommend in my Risk-Based CAPA webinar.

Recommendations for Trend Analysis

Whenever you establish a new metric or quality objective, you should also establish a limit for when you intend to investigate and when you intend to take preventive or corrective actions. If you simply start measuring a variable or attribute, you may have difficulty recommending actions to management during your next management review and explaining why actions were not taken during an FDA inspection or an audit.

Additional Related Reading
If you are interested in reading more about how this might be applied to inspection results, please read my blog titled, “21 CFR 820.80: 3 Ways to Record Inspection Results.”

Posted in: CAPA

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DHF Template – Format and Content of Design History File

The article does not include a DHF template, but recommendations for format and content of a design history file are provided.

DHF Content DHF Template   Format and Content of Design History File

A couple of weeks ago I announced that I will be conducting a webinar today (i.e., 10:00am EDT on April 14, 2016) on the topic of the design history file (DHF). One of my blog readers sent me an email in response to this announcement requesting a DHF template.

Regulatory Requirements for a Design History File (DHF)

The requirements for a design history file (DHF) are found in 21 CFR 820.30j: “Each manufacturer shall establish and maintain a DHF for each type of device. The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of this part.“ There is also a definition for a DHF found in 21 CFR 820.3(e), “Design history file (DHF ) means a compilation of records which describes the design history of a finished device.” The FDA provided an official interpretation of this requirement in the preamble when the QSR was published in 1996. That discussion of the requirement indicated that the DHF is intended to be a repository of the records required to demonstrate compliance with your design plan and your design control procedures. The discussion also indicates that the same DHF may be used for minor variations of a device such as size differences. Most manufacturers will organize the DHF in a binder and organize the binder chronologically to match a design project plan. Meeting minutes from each design meeting are typically included as an appendix to the DHF, while reviewed and approved documents such as the design plan, design inputs, design outputs and records of design reviews typically comprise the bulk of the DHF. Manufacturers also typically will conduct an internal auditor of active DHF binders in order to ensure that design projects are following the approved design plans.

Why a DHF Template Doesn’t Make Sense

The DHF is is intended to provide evidence of following an approved design plan, but the DHF consists of many records–not just one record. A DHF template could be created to follow a standardized design control process, but most manufacturers write a generic design procedure that allows and encourages the design team to customize the design plan to match the needs of each development project. Therefore, design plans may have different numbers of design reviews and very different testing activities prior to the start of the design transfer process and during design verification and validation.

For a device master record (DMR), I recommend creating a DMR Index using a template that is organized in accordance with an international standard to meet the needs of a DMR and a Technical File. However, the DMR is a living document that only shows the most current design outputs for a device while a DHF may require repeating various verification and validation testing if the initial design fails to meet acceptance criteria and a design change is required prior to the final design review and approval of commercial release. The need for including this variability eliminates the advantages of a template.

Documenting Design Changes in the DHF vs. the DMR Index

Product design changes that occur prior to the final design review and approval of commercial release are required for inclusion in the DHF. However, once a product is released the control over design changes should be tighter and regulatory submission of changes may be required. Therefore, I recommend documenting post-market design changes in the DMR Index for a device as part of the revision history. I treat the DMR Index as a controlled document and any post-market design changes are reflected in the revision history with a reference to the design change approval (e.g., ECN 123 – addition of UDI label to product labeling). The other advantage of this approach is that all post-market design changes that must be documented for a design dossier are summarized in the revision history of the DMR Index and the DMR Index will serve as a Technical File/Design Dossier.

Design History File (DHF) Webinar

If you are interested in learning more about design history files, there is still time to register for today’s live training webinar. For a cost of $129 you will receive:

  • a link to join the live webinar @ 10am EDT
  • a native slide deck for the new live webinar
  • a link to download a recording of the live webinar

This live webinar explains what needs to be included in your procedures for design and development, but the webinar explains how and when to create a design history file (DHF). After you create a procedure, you can show the recording of this webinar to your design and development team to ensure that design and development documentation is compliant and updates are efficiently maintained.

After 9:30am EST, you will be able to purchase the webinar as recording only.

CLICK HERE to register for the live DHF webinar or to purchase the recording.

Posted in: Design Control

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Class 1 Device Requires Clinical Evaluation Report (CER) too!

Article explains how to write a clinical evaluation report (CER) for CE Marking Class 1 medical devices when there is little or no clinical study literature available. The history behind this European CE Marking regulatory requirement is explained as well.

Clinical study for this  e1446901425122 Class 1 Device Requires Clinical Evaluation Report (CER) too!

In 2010 the European Medical Device Directive was updated to include many tougher regulatory requirements for medical devices of all types. One of this changes is criticized frequently by industry–the change to make essential requirement 14 to a general requirement for all devices. That requirement is now essential requirement 6a in Annex I of the current MDD (93/42/EEC as modified by 2007/47/EC). The general requirements are required for all devices–event products that do not require a Notified Body’s involvement.

Typical Search Strategy for a Class 1 Device

Class 1 devices do not typically have clinical studies performed for three reasons:

  1. the products are low in risk and therefore do not require clinical studies for regulatory approval
  2. the products have been on the market for a long time and therefore there is little innovation in these products
  3. clinical investigators are not interested in researching devices that have been used for a long time

Since there is typically no requirement for a clinical study for a Class 1 device, companies will perform a literature search in order to meet the requirements of Essential Requirement 6a. That search will typically result in articles that mention the device or a competitor device, but the device is typically just part of a clinical study that was performed for another device (i.e., the device of interest is merely an accessory). If there are clinical studies, the studies may be quite old and it may be more helpful to search for review articles first. In the end, you may end up finding no clinical studies for the type of device you are designing, but a clinical evaluation report is still required for CE Marking for Class 1 devices.

It may be painful for you and your company to conduct a clinical evaluation, even using the literature route, when there are no new clinical studies to find. However, the CE Marking regulations are written to address all devices and material innovations alone are driving the need for companies to reconsider the “state of the art” for even Class 1 devices. It is also important to consider emerging issues such as infection control with antibiotic resistant strains and the trend toward using disposable instruments such as drill bits.

Reference Articles for Clinical Evaluation Reports and PMS

I have published 3 previous blogs specifically on the topic of clinical studies and post-market surveillance over the past couple of years. Please click here if you are looking for more information on this topic.

Procedure/Template for Class 1 Device Clinical Evaluation Report (CER)

If you are looking for a procedure (SOP) and associated literature search protocol template for a clinical evaluation report (CER) please click here. The purpose of this 6-page procedure is to define the process for performing a clinical evaluation of literature in accordance with MEDDEV 2.7/1. There is also template provided for performing a literature search (i.e., TMP-004).

Posted in: Clinical Studies & Post-Market Surveillance

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What are the most common FDA Form 483s inspection observations?

I recently had a couple of clients request a quotation for training on best practices for creating a design history file (DHF). Typically the most experienced quality managers request this training, even when they personally know a lot about design controls, because they know that the FDA issues a lot of FDA Form 483s against this requirement.

The most frequent category of FDA Form 483 inspection observation is design controls (i.e., 21 CFR 820.30). There are 10 different sections of the design controls requirement. Manufacturers that do not have design controls in place will frequently receive multiple observation findings during the same inspection–all related to design controls. The most common design control observations are:

  1. A procedure for design and development has not been established in accordance with 21 CFR 820.30a
  2. A procedure for design transfer has not been established in accordance with 21 CFR 820.30h
  3. A procedure for design changes has not been established in accordance with 21 CFR 820.30i
  4. A design history file (DHF) has not been established in accordance with 21 CFR 820.30j

Therefore, if a manufacturer has no procedure for design controls, then the manufacturer could receive 4 different observations on FDA Form 483.

ISO 13485:2016 Requirements

On March 1, 2016 the 2016 version of ISO 13485 was released. The new version of the Standard now requires procedures for design transfer, design changes and design and development files in an effort to be harmonized further with US regulatory requirements. Therefore, this presentation was created to specifically identify changes needed to your design controls procedure in order to comply with the latest version of the Standard.​​​​​​​

Design History File (DHF) Webinar

You can register for this live training webinar on April 14. For a cost of $129 you will receive:

  • a link to join the live webinar @ 10am EDT
  • a native slide deck for the new live webinar
  • a link to download a recording of the live webinar

This live webinar explains what needs to be included in your procedures for design and development, but the webinar explains how and when to create a design history file (DHF). After you create a procedure, you can show the recording of this webinar to your design and development team to ensure that design and development documentation is compliant and updates are efficiently maintained.

CLICK HERE to register for the DHF Webinar.

Posted in: Uncategorized

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483 Response: Which corrective action plan should you write first?

Article explains how to determine which FDA Form 483 response you should write a corrective action plan for first and why.

chicken and egg 483 Response: Which corrective action plan should you write first?

In a perfect world, you would not receive any inspection observations from your next FDA inspection. However, most companies get at least one observation resulting from an FDA inspection and often there are multiple observations on an FDA Form 483. If you

Most Common FDA 483 inspection observation

Companies that have not experienced an FDA inspection before worry too much and prepare too little. Inspections are predictable and certain inspection observations are much more common than others. A couple of years ago I wrote an article analyzing the most common FDA inspection observations. The most common observations are specific to design controls (i.e., 21 CFR 820.30). However, this fact is distorted because many companies receive multiple observations during the same inspection related to design controls. For example, a client of mine recently received three from one inspector: 1) lack of design reviews, 2) lack of design validation, and 3) lack of risk analysis. All three were found during the review of the same design history file and the one corrective action addresses all three observations.

how to determine which FDA Form 483 response you should write a corrective action plan for first

2nd Most Common FDA 483 inspection observation

The second most common observation is specific to corrective and preventive actions (i.e., 21 CFR 820.100). Typically the company has inadequate procedures for verifying and validating effectiveness of corrective actions taken. If this is one of your FDA 483 observations, then you may have a problem with CAPA training or with the design of your CAPA form. If there is no place on the CAPA form to document your effectiveness check, then you might easily forget to perform the verification and validation of effectiveness. Another possibility is that personnel are confused between verification of implementation and the verification of effectiveness.

What if you have multiple FDA 483 observations?

Other common FDA 483 observations include medical device reporting, complaint handling and rework of nonconforming product. If you receive more than one FDA 483 inspection observation, you need to assume there is a chance that the inspection outcome will be “Official Action Indicated” (OAI). In this case, you need to provide a 483 response to your FDA district office within 15 business days. With such a short time to prepare your 483 response, you need to be efficient. Which 483 response should you initiate first and why?

If one of the inspection observations is related to the CAPA process, that 483 response should be your top priority. The reason for this is that the FDA will want to see objective evidence of implementing corrective actions whenever possible. If you use your CAPA procedure and form to document the 483 response, then you can show the FDA how the revised procedure or form will be used in your 483 response. If you write your 483 response for other inspection observations first, then the other 483 responses are using the existing procedure or form that the identified as inadequate.

Your first step should always be to implement corrective actions to address an inadequate CAPA process by revising the procedure or the form. Once the procedure or form is updated, then you can use the new process to document the rest of your 483 responses.

Training Webinar for an FDA 483 response

If you need help preparing an FDA 483 response, click here for our webinar explaining the 7 steps for responding to an FDA Form 483 inspection observation. You can also download a CAPA procedure and CAPA form from our SOP page.

Posted in: FDA

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