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New FDA Guidance documents for combination drug/device products, medical devices, and FDA inspection trends.

What is the mdsap pilot?

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This article explains what is the MDSAP pilot, and how is the pilot program likely to impact medical device manufacturers.

robs mdsap logo What is the mdsap pilot?

The acronym “MDSAP” stands for “medical device single audit program.” This is a three-year pilot program that began on January 1, 2014. Regulatory bodies are attempting to use a single regulatory audit to meet the requirements for all countries. The MDSAP pilot is one of the direct results of medical device regulatory bodies forming the new International Medical Device Regulators Forum (IMDRF) organization (http://bit.ly/imdrf).

The FDA’s Kim Trautman is the working group chairperson for IMDRF. There is a limited amount of information on the IMDRF webpage (http://bit.ly/imdrf-mdsap), but you can find more information on the US FDA website (http://bit.ly/MDSAP). Four countries are currently participating in the MDSAP pilot:

Japan is an official observer for the program, with the participation of both their device agency (http://bit.ly/Japan-MHLW) and pharmaceutical agency (http://bit.ly/Japan-PMDA). China and Europe are also represented in the mdsap working group at the IMDRF.

Currently, there are 15 recognized registrars for the CMDCAS (http://bit.ly/CMDCAS-webinar) program for medical device companies that want to obtain a medical device license in Canada. Health Canada plans to participate in the mdsap pilot for three years, and then the MDSAP program will become a mandatory replacement for the CMDCAS certification program in 2017.

How will auditors approach MDSAP audits?

The current CMDCAS audit program benefits significantly from Health Canada’s alignment of the Canadian Medical Device Regulations (CMDR) with the ISO 13485 Standard used by third-party auditors. The tool that Health Canada uses to ensure that auditors are consistent is the GD210 audit checklist (http://bit.ly/GD210Guidance). The MDSAP will need to harmonize the regulations of Canada, Australia, Brazil, and the USA. This may seem like an impossible task, but Notified Bodies and consultants have been using multi-national regulatory comparison checklists for years to ensure that all the applicable regulations are covered during audits.

Auditors currently relying primarily upon audit checklists should quickly adapt to the MDSAP with longer lists. However, those third-party auditors that are now using the process approach will need to study the comparison checklists being developed carefully. The process approach will still be the best approach for auditing. Still, auditors will need to be familiar with a larger number of requirements for step in the population of their turtle diagrams (http://bit.ly/Process-Approach).

I recommend looking at what aerospace and automotive auditors do. Auditees are expected to create and maintain process flow charts for each process, but the auditors will also compare previous versions they created in past audits. This makes the process much more efficient–except the first time they create the diagrams.

How will MDSAP audits be different?

The biggest difference between the current CMDCAS audits and the MDSAP will be the duration of audits. SGS indicated on its website (http://bit.ly/MDSAP-SGS) that manufacturers should expect these audits to be 35-100% longer in duration. The typical ISO 13485 audit might be two days, and CMDCAS might add no additional time or as much as a half-day to the duration. However, the MDSAP program will require gathering objective evidence for Australian, Brazilian, and U.S. regulations. Even if this only added a half-day for each country, the combined effect would be four days instead of two and one-half days.

At first glance, this may seem to be a burden, but this should be a relief. Currently, manufacturers might have a CMDCAS audit every year, an FDA inspection every other year, and they are still waiting for an ANVISA inspection so that they can launch a product in Brazil. Instead of a worst-case scenario of three audits/inspections in one year, the MDSAP program will enable companies to schedule a single audit to address each major market at one time. When Japanese and Europeans adopt the MDSAP as well, then companies will realize an even greater overall reduction in the number of audit days each year.

How important will the MDSAP pilot be?

Historically, Health Canada is the only country that made ISO 13485 certification mandatory. However, making ISO 13485 certification mandatory essentially made ISO 13485 a global prerequisite for medical device manufacturers–which has not happened with ISO 9001 certification. Health Canada indicated that it intends to make the MDSAP program mandatory at the end of the 3-year pilot. If Health Canada makes MDSAP audits mandatory, MDSAP may become the new defector auditing standard globally.

In addition to the impact of Health Canada, Brazil has agreed to accept the MDSAP audits instead of initial audits by ANVISA. The current backlog of ANVISA audits more than a year, and companies have resorted to filing lawsuits against ANVISA to get to the “top of the list.” Therefore, all of the companies on the waiting list are likely to jump at the opportunity to participate in the MDSAP pilot.

Let me know if you want to understand specifics about the MDSAP program. Please submit your suggestions for future blogs to our suggestion portal.

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UDI Implementation-Why You Need to Begin Today

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udi UDI Implementation Why You Need to Begin Today

In this blog, “UDI Implementation-Why You Need to Begin Today,” the author provides reasons why you should begin your implementation today and the benefits of doing so.

I have taken you through what UDI is, what you need to do to meet its compliance dates, and in the last few blogs, written about the steps you need to take to implement UDI in your organization. With the September 24, 2014 deadline looming, labelers of Class III devices and stand-alone software should be well on their way with implementation. But what about you who label implantable, life-sustaining, life-supporting (9/24/15 deadline), Class II (9/24/16 deadline), or Class I (9/24/18 deadline) devices? Should you wait or begin now?

UDI – Good Business Sense

There are many reasons why implementing UDI makes very good business sense. Two overriding reasons are increased revenues and lower costs. The healthcare industry has been using Automated Identification and Data Capture (AIDC) technology for a number of years. FDA has required since 2004, drug manufacturers use barcodes (NDC number) on their  labels. Now, they require device manufacturers (labelers) use Unique Device Identifiers (UDI) on their medical device labels. 

Hospitals and Group Purchasing Organizations (GPOs) have been at the forefront of persuading many medical device manufacturers to adopt UI for the devices they label. GPOs are now at the point of mandating manufacturers to implement UI to continue and/or obtain contracts to sell their devices to GPO hospital members. Even with that significant pressure, many manufacturers have resisted implementing UI. Of course, now, they will have no choice.

UDI Implementation-Why You Need to Begin Today

Manufacturers who have implemented UI have seen increased revenues and decreased costs. Their hospital/GPO customers view them as “easy-to-do” business with, resulting not only in an increase of sales of contracted devices but also of non-contracted devices. Hospitals must implement systems to reduce their costs. UDI is such a system. It will permit hospitals to manage their inventories better, reducing or eliminating product duplication, as well as realizing improved inventory tracking.

The use of product barcodes will allow hospitals to charge patients more accurately for the devices they use while hospitalized. Manufacturers have also been able to increase the speed to market for a new device compliant with UI, and by adding it to their existing GPO contracts. This can increase the new device’s exposure to the market very quickly.

Becton Dickinson Implementation

The March 2011 Edition of Healthcare Purchasing News published an article by Karen Conway that describes Becton, Dickinson, and Company (BD) Resource Optimization and Innovation (ROi) experiences implementing UI (GS1’s Global Trade Identification Number). Dennis Black (BD) and Alex Zimmerman (ROi) describe the positive impact implementing UI had on their businesses.  They were able to document a 30% reduction in accounts payable days outstanding. Other findings included:

  • 73% reduction in errors on customer orders
  • fewer stock-outs
  • greater process efficiency
  • fewer calls to customer service
  • better charge compliance

All are excellent reasons to start UDI implementation now.

Regulatory Affairs will also benefit from implementing UDIs. Improving the recall process will help reduce costs through easier tracking of which customers to contact, versus what is typically a very arduous and time-consuming process today. Starting now will also allow you to control the pace of the required changes to your organization, and collect data needed to submit to GUDID. This regulation will put your organization under a tremendous amount of pressure without having to deal with the crisis of a short implementation window.

The most common mistake I have seen organizations make is poor planning around UDI implementation. They significantly underestimate the amount of time it will take to implement UDI, the amount of change that will occur within the organization to be compliant, and being able to manage the ongoing requirements of UDI. These issues are compounded for multi-site organizations, where project planning is critical. 

Earlier in this blog, I mentioned hospitals using barcodes to charge fees for devices used by patients. This information will be added to the patient’s electronic health record. From there, this information will work its way into large population databases, such as claim data. Manufacturers will ultimately be able to use this claim data to identify new potential intended uses for products, and thereby expand their target markets.

Implementing UDI now makes good business sense. Why wait and put your organization in jeopardy?

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Obtaining an FDA Certificate to Foreign Government for Medical Devices

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certificate to foreign gov Obtaining an FDA Certificate to Foreign Government for Medical DevicesThis article explains how to obtain an FDA Certificate to Foreign Government when you are trying to submit an application for registration of a medical device to a regulatory body outside the United States (e.g., COFEPRIS approval for exports to Mexico).

What is an FDA Certificate to Foreign Government?

If you have a medical device that is registered and listed with the US FDA, then you can obtain a Certificate to Foreign Government from the US FDA. A Certificate to Foreign Government is a certificate issued by the US FDA verifying that your company may legally export the device, and the device may be distributed in the United States. Regulatory bodies in some countries request a “Certificate of Free Sale.” Still, these are issued by the US FDA for foods, while the agency issues Certificates to Foreign Governments for medical devices. The name of the certificate is not the same for all countries, and regulators use the terminology most familiar to their country. The US FDA has more information about the different types of certificates on the following FDA webpage: http://bit.ly/FDA-Export-Certificates.

How do you obtain a Certificate to Foreign Government?

The following page on the FDA website answers common questions about exporting medical devices. http://bit.ly/Exporting-Medical-Devices. One of the most common requirements of foreign registrations is providing a Certificate to Foreign Government. If your product is currently registered and listed with the US FDA, you are managing your registration and listing using an FDA Unified Registration and Listings System (FURLS) account (http://bit.ly/registration-listing-blog). Through this account, you can access the new CDRH Export Certification and Tracking System (CECATS). CECATS allows manufacturers to request export documents, including Certificates to Foreign Governments, online versus paper submissions. CECATS reduces certificate processing time and will enable you to validate firm-specific data in real-time. You can also obtain a status update for your certificate request. If you have additional questions about CECATS or export certificates, the FDA also created an Exporting FAQs page: http://bit.ly/Exporting-FAQs.

How much does a Certificate to Foreign Government Cost?

Certificates to Foreign Government are product specific and cost $175 for the original certificate. Each additional copy (official copies from the FDA are usually required) costs $15 per copy. Up to 50 pages (including the certificate, manufacturer page, and attachment pages) may be submitted for the same product. Each time an increment of 50 pages is exceeded, an additional fee of $175 will be charged.

If the original is three pages long and you request an original and ten copies (33 total pages), then your charge will be $175 for the original and $150 for the ten copies–a combined total of $325. However, an original and 20 copies (63 pages) would exceed the 50-page limit, and you would be charged $175 for the first original and $225 for the first 15 copies. You would then be charged $175 for a second original and another $60 for four more copies.

Don’t wait until the last minute to request Certificates to Foreign Governments. I recommend ordering 5-10 copies when you first register a product in the FURLS database, instead of waiting until you need it. The same is true of other types of certificates, such as CE Marking certificates from your Notified Body.

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9 Major Steps That Should Be In Your UDI Implementation Plan

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steps udi 9 Major Steps That Should Be In Your UDI Implementation PlanIn the last blog, I started the discussion on UDI implementation and how it will impact nearly every area of your company. Successful implementation will take careful planning and coordination throughout the organization and, in some cases, outside your company. As with every other FDA regulation, you will need to have resources available to maintain and update your systems; plus, you will need resources to update and maintain the Global UDI Database (GUDID). 

 What Comes Next?

The UDI regulation is a maze. In trying to solve a maze, it is often easier to start at the end. This same philosophy should be used to implement UDI in your company. Start your implementation process with the outcome in mind. It is more than simply meeting a timeline. UDI implementation should be viewed as a way to improve your business with the daily processes you use. It should help you standardize your daily processes, especially regarding data gathering, label design, and communication with your trading partners. This process will yield helpful marketing information, one of the most outstanding values resulting from implementing a UDI system.

Create an Implementation Playbook

Creating a playbook or strategic plan is a necessary step. Without one, your hope of successfully implementing UDI requirements will be severely reduced. Your playbook should focus on solving real business problems within your organization. Issues such as how will you collect missing data? Create a “label brand” through standardization. Are you able to develop a cross-functional team for implementation and beyond? Can you streamline your labeling and packing functions? What can other processes be improved? The playbook you create must be tailored to solve your organization’s issues.

Now the Specifics

Implementing the strategic plan for your organization requires coordination of UDI-related activities from all impacted areas identified in your plan. In addition to having an overall UDI leader, each area should have a designated person responsible for ensuring the tasks assigned to their area are completed. The significant steps of each plan should include:

1. Acquire missing data attributes and create a data management process

o   Develop a protocol for obtaining missing attributes

o   Determine who is responsible for compiling the information

o   Determine who is responsible for managing the collected information

    • Enter into Excel spreadsheet

o   Establish a verification and validation process

o   Determine who is responsible for validating the information

    • Review source documents against gathered information

2. Amend label/packaging composition and components; order by the device compliance date

o   Develop label template for the entire organization

o   Develop a label sign-off process to include all impacted areas

o   ADIC Technology will work for you? Concatenated, Stacked, 2-D Matrix? What are the technical capabilities of your trading partners? 

o   What packaging changes are required to accommodate new labels?

o   Determine what the global considerations for label changes are. Do other regulatory agencies need to approve label changes? Will amend or new device submissions be required?

3. Compose, create, administer, and verify/validate software system changes and integrations

o   Does 21 CFR Part 11 apply to these changes?

4. Acquire new or upgrade existing labeling and packaging equipment and verify/validate

o   Does 21 CFR Part 11 apply?

5. Rehearse connectivity with GUDID and verify all systems are functioning correctly

o   Does 21 CFR Part 11 apply?

6. If required, plan for Direct Marking requirements

     o   Obtain etching equipment appropriate for your devices

7. Create/revise Quality System SOPs as needed and conduct process validation

8. Determine if, as part of your strategic plan, your company should invest in building inventory levels – using the three (3)-year extension period for inventory labeled before the compliance date – to create a buffer in case implementation is delayed.

9. Develop training programs to train staff on new responsibilities in maintaining the UDI system. Whether the outcome of your implementation is successful or not is directly tied to how well your team plans and executes. Validation of the changes becomes a significant aspect of the implementation process and cannot be taken lightly. Remember the adage – “Garbage in, garbage out.” But in this case, there are serious ramifications for “Garbage in.”

UDI – the Forever Project

UDI is not a “one-and-done” project. The entire system will need continual maintenance. Computer systems will need constant updating as changes to devices or new ones are developed. It would be best to appoint someone with clear responsibility for maintaining your information in GUDID. Postmarket surveillance activities also feed into the post-implementation process, as device changes are made due to tracking and reporting activities. And you will find that you will continually need to train your staff on UDI requirements, especially with staff turnover.

The actual value is not in the barcode; it is the DATA that will be generated from using barcodes.   Finally, identify the appropriate value proposition for your organization, and remember that in healthcare, there is no single answer for all situations.       

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5 Classic blunders that result in an fda warning letter from CDRH

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FDA Warning 5 Classic blunders that result in an fda warning letter from CDRHThis blog reviews 5 of the most common reasons for why CDRH issues FDA warning letters and preventive actions are suggested for each of the five reasons.

The following is a quote from an interview I conducted with a former FDA inspector:

“You’re in deep trouble if the [FDA 483] response is excellent, and the corrective actions are excellent, but when the FDA comes back, you never bothered to implement those corrective actions. Now you know that you have that warning letter coming at you.”

#1 – No actions implemented for CAPAs

The former inspector describes one of the most common reasons for FDA warning letters. If an FDA investigator issues an FDA 483, you must respond with a corrective action plan (FDA-483). However, you must implement your plan to close the FDA 483 inspection observation(s) during the next FDA inspection. CDRH’s QSIT inspection manual (http://bit.ly/QSITManual) requires that the CAPA process be evaluated during every inspection–even during abbreviated inspections, where only two of the four major quality subsystems are sampled (i.e., “CAPA + 1”). Therefore, the FDA investigator will notice if no actions have been taken for CAPAs that were initiated since the last inspection. If the CAPAs are specific to the FDA 483–CDRH requires the FDA investigator to review those records first. To ensure that corrective actions are being implemented and documented, I recommend three ways of controlling the process:

  1. monitor the “aging” of CAPAs and establish a quality objective for average days aging
  2. have an independent expert perform a desktop audit of your CAPA process
  3. ensure that you carefully review each CAPA that is behind schedule during Management Reviews (which should be at least quarterly)

#2 – FDA 483 response submitted late

A second common reason for receiving an FDA warning letter is a failure to submit an FDA 483 response to the district office within 15 business days. The FDA has always involuntarily required a medical device firm to respond to an FDA 483 within 15 business days, but in 2009, a post-inspection review program (http://bit.ly/15Dayresponse) was initiated where it became mandatory that a response from any FDA 483 must be received by the Agency within 15 business days, or FDA warning letters are automatically issued. This is an automatic issuance that results in a very quick response from your CDRH district office. Therefore, you need to respond aggressively to FDA 483s with corrective actions and submit your response early.

Note: The FDA warning letters are only issued when inspection observations result in an “Official Action Indicated” (OAI). However, inspectors will not tell you if the outcome is OAI or Voluntary Action Indicated (VAI). This determination is made by the District Office of the FDA. Therefore, all device manufacturers should assume that the outcome may be OAI.

#3 – Submitting a response without evidence of implementing changes

This past Saturday, I recorded a webinar on the “7 Steps to Respond to an FDA 483 Inspection Observation” (http://bit.ly/FDA-483-response-webinar). The title of the third slide in that presentation is “The FDA may be late…”. I mentioned that it is not uncommon for FDA warning letters to be issued six months after the actual inspection occurred. The following warning letter is an example (http://bit.ly/fda-warning-letters-example1).

I don’t personally know this firm, but I found this example by searching through the FDA warning letters database: http://bit.ly/fda-warning-letter-search. The company received an FDA 483 with multiple inspection observations on November 4, 2010. The company was non-compliant in the following areas: CAPA (21 CFR 820.100), complaint handling (21 CFR 820.198), and design controls (21 CFR 820.30). The company responded to CDRH on November 23. This was 13 business days after the FDA 483 was received, and with FedEx shipping, it probably arrived at the FDA barely in time–November 29 (the Monday after Thanksgiving).

Unfortunately, the response did not include evidence of correcting the existing procedure deficiencies. The plan indicated changes were going to be made, but the FDA expects you to revise procedure deficiencies quickly (i.e. before you mail the response to the FDA 483). If it is impossible to make corrections in this timeframe, a risk-based approach is recommended. For example, the complaint handling process is the most critical of the three processes identified as deficient in the warning letter. Therefore, the company should have enclosed a revised complaint handling procedure and promised to revise the CAPA and design control procedures within a few weeks.

The FDA warning letter was not issued for this example until April 6, 2011–almost six (6) months from the date of the FDA 483 issuance. CDRH offices are ghost towns in December. Therefore, it was important for the company to contact CHRH early in November to identify an email address and contact to send documentation regarding implementing corrective actions. The company could have revised the other two procedures in December and implemented all three procedures in December. Evidence of thorough implementation of corrections and corrective actions by email is often adequate to prevent FDA warning letters.

This is extremely important for international firms because a second warning letter for an international firm results in a warning letter with automatic detention (i.e., the company cannot import a product into the USA). In this example, the second warning letter was issued on November 26, 2012 (http://bit.ly/fda-warning-letters-example2).

#4 – Failure to remove objectionable marketing communications

The FDA does not routinely visit companies that only manufacture Class 1 (i.e., low-risk) devices. However, they routinely visit companies that manufacture medium-risk, Class 2 devices. The FDA reviews websites and other marketing communications for marketing claims that are not within the scope of an issued 510k. Typically, the claims that are allowed are almost verbatim from 21 CFR (i.e., Title 21 Code of Federal Regulations). Therefore, many companies receive an FDA 483 indicating that they are claiming an indication for the use of which the device does not have clearance (i.e., a 510k). The company is expected to remove the claims and/or submit a 510k in these cases. In these cases, CDRH will often wait a year or more before taking additional action to give the firm ample time to obtain clearance for the indications. Here is a link to an example of a warning letter of this type: http://bit.ly/fda-warning-letters-example3.

#5 – Design controls are not implemented at all

Design controls are the most common reason for the issuance of an FDA 483 (483-Data-Analysis). If you read the blog, Medical Device Academy wrote on the data analysis of FDA 483 inspection observations issued in FY2013 by CDRH, and you may have wondered how design controls are the #1 most common FDA 483. Still, the highest individual clause reference is #8 [i.e., 21 CFR 820.30(i)]. Reviewing this next warning letter example (http://bit.ly/fda-warning-letters-example4), it should become clear that some companies do not have a design control process implemented. In this situation, the FDA investigator is likely to issue a separate FDA 483 against each of the required elements:

  1. 21 CFR 820.30(e) – design reviews
  2. 21 CFR 820.30(f) – design verification
  3. 21 CFR 820.30(g) – design validation
  4. 21 CFR 820.30(h) – design transfer
  5. 21 CFR 820.30(i) – design changes

In this specific example, the FDA investigator issued the FDA 483 on August 16, 2012, and the warning letter was issued immediately after the FDA returned from the holidays–January 4, 2013. This firm had a narrow window of time between August and November to submit an FDA 483 response and then follow up with documentation of completing the CAPA plan. The warning letter indicates that the corrective action plan was inadequate, but the FDA still took several months to issue the warning letter.

If you recently had an FDA inspection and received an FDA 483, ensure you don’t make any of the above mistakes. You might also want to take the webinar on this topic: http://bit.ly/FDA-483-response-webinar.

If it’s been a year since you received an FDA inspection, you might want to watch the video on this webpage: regulatory-compliance-services

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7 Steps to writing an FDA 483 response

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Responding in 15 business days is one of 7 steps on how to write an FDA 483 response, but do you know what should be in your response?7 steps fda 483 blog 7 Steps to writing an FDA 483 responseWhen an FDA investigator has an inspection observation, the investigator issues an FDA 483. “Form 483” is the FDA form number. If your company receives an FDA 483, it is critical to understand how to write your FDA 483 response in order to avoid a Warning Letter. In the words of a former FDA investigator, “Many, many times I have seen an [Official Action Indicated (OAI)] classified inspection that had been recommended for a Warning Letter by the compliance branch be set aside based upon the response of the firm.”

The best way for your company to write a FDA 483 response is to provide a brief cover letter and to use your CAPA process. Every 483 inspection observation needs to be addressed in the FDA 483 response as a separate CAPA. Make sure that your response includes the following seven steps below:

  1. respond within 15 business days (earlier is better)
  2. use your CAPA form and a cover letter–instead of a memo
  3. document the investigation that was conducted with a concisely stated root cause
  4. identify containment measures and corrections to address each specific observation by the FDA inspector
  5. identify corrective actions planned and the date(s) you expect to complete implementation
  6. Include documentation of containment, corrections and corrective actions that are completed at the time you submit the response
  7. follow-up with a memo confirming that all the corrective actions are complete and include all related documentation–including training for any new procedures or any new corrective actions that warranted training

Your FDA 483 response is required in less than 15 business days

The FDA has always involuntarily required a medical device firm, or any firm under FDA jurisdiction that received an FDA 483, to provide a written FDA 483 response to the District Office within 15 business days. As of two years ago (http://www.gpo.gov/fdsys/pkg/FR-2009-08-11/pdf/E9-19107.pdf), it became mandatory that the Agency must receive a FDA 483 response within 15 business days, or an automatic Warning Letter is issued. You need to respond aggressively to FDA 483s with corrective actions, and submit your response early. The FDA has also modified the format of the response to require email responses.

Use your CAPA forms instead of a memo.

I have asked several former FDA investigators whether they would prefer to see firms submit responses in memo format, or by using their CAPA forms and a cover letter. Some told me that they prefer to see firms use their CAPA forms, while others don’t seem to have a preference. Nobody from the FDA has ever indicated a preference for a memo. I see no point in doubling your work and risking transcription errors. If you have an electronic system that does not have an easy-to-follow output format, go ahead and copy-and-paste the information from your electronic database to your memo. If the CAPA system output is easy to follow, just use a cover letter and copies of the forms.

Document the investigation and root cause

This is definitely my pet-peeve, but a one-sentence “root cause” is not enough for an FDA 483 response. Regardless of whether I am doing a mock-FDA inspection, an internal audit, or a supplier audit–I expect you to document how you determined the root cause (http://robertpackard.wpengine.com/five-tools-for-conducting-root-cause-analysis/). If it’s trivial and obvious, then it must have been something important, or I would not have written a nonconformity. Therefore, you should be looking beyond the immediate scope of the FDA 483 to ensure that a similar problem cannot occur elsewhere. In the language of the FDA, this is a preventive action, because you are preventing occurrence with another process or product. Most ISO certification auditors are purists, and they won’t accept this as a preventive action. You will have to show the purists something special–maybe from your data analysis.

Don’t forget containment and correction

For every 483 observation, including the subparts, you need to identify if immediate containment is necessary and how you can correct the problem. Whenever possible, you should attempt to implement the containment and corrections during your FDA inspection. It would be fantastic to give the FDA inspector a copy of the new CAPA you initiated during the audit. The new CAPA would identify containment and corrections that have been or will be implemented–including any nonconformity(s) you initiated to quarantine product. You may still get an FDA 483 inspection observation, but you are likely to convert a possible Official Action Indicated (OAI) into a Voluntary Action Indicated (VAI). You can also modify the CAPA wording later in your FDA 483 response to include a cross-reference to the FDA 483 and quote the exact wording the inspector uses.

Explain the corrective action plans and timelines

Clarity, brevity, and realistic plans are critical in this section of your response. I prefer a table that looks like the example shown below.

7 steps 483 chart 7 Steps to writing an FDA 483 response

Show the FDA you have already taken action in your FDA 483 response

Whenever possible, you want to show the FDA that you are taking action without delay. If you revised the SOP for MDRs and scheduled a group training for July 15, then you should provide the FDA a copy of the revised procedure and a copy of the agenda for your planned training session. The only caution is to only commit to actions you are certain you will implement. You can always do more, but it will be much harder to explain why you did not implement an action you submitted in your FDA 483 response.

Follow-up with a second FDA 483 response before the FDA asks for it

The FDA’s compliance office will be looking for a response when an FDA 483 is issued, and they will review your response. The investigator will get a copy of the FDA 483 response, and the investigator will comment on the response. The compliance office and the investigator enter their comments into a CDRH database. Still, the comments are only general, as to whether the response is adequate or inadequate and will require additional review.

If you do not hear back from the FDA, do not assume that the compliance office or the investigator was satisfied. You should also follow-up several months later (earlier if possible) with a letter that includes evidence of the completed corrective actions, and your verification of effectiveness. If the verification is compelling and received in less than six months of the inspection, you may convince the compliance office to hold off a planned Warning Letter.

If you are interested in root cause analysis and improving your CAPA process, we have two related webinars:

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The First 4 Steps of Unique Device Identification Implementation

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fda udi clock The First 4 Steps of Unique Device Identification Implementation

In this blog, the author explains the first four steps of the Unique Device Identification system implementation and why they are essential.

UDI implementation will impact nearly every area of your company. Successful implementation will require careful planning and coordination throughout the organization and, in some cases, outside your company. You will need to assign resources to update and maintain your systems and the Global UDI Database (GUDID).

The Commitment to Begin is Step 1

The first implementation step is committing to begin. Unique Device Identification (UDI) systems have been used in healthcare for many years, especially for over-the-counter products (commonly known as “UPCs”). Many companies have already implemented UDI systems using one or more of the Issuing Agencies’ protocols. They understood the benefits of moving forward with developing UDI capabilities in advance of any regulatory requirements. Customers also played a role in influencing early adopters of UDI. Customers told companies to employ standardized methods, such as UDI. Otherwise, they would stop buying their products. The fear of losing a customer is a powerful incentive, but early adopters also understood the additional benefits of being an early adopter of UDI–including:

  • Ability to control the pace of implementation without having to be concerned with mandated timelines
  • Becoming “easy to do business with.”
  • Reduction in transaction errors
  • Decreased order-to-cash process time
  • Help customers ensure patients receive the correct products
  • Reduce costs associated with product recalls and other business processes
  • Increase patient safety and satisfaction
  • Reduce waste through better inventory management throughout the supply chain.
  • Increase revenue through greater product line exposure to the customer base.
  • Increase the speed-to-market of new devices.

FDA regulation has now mandated UDI implementation for most medical device labelers. Compliance dates are established. If you miss the date(s) relevant to your devices, you can no longer legally sell your medical devices. Why wait? Start the implementation process now.

Now what? The second step…

Since UDI implementation is a significant undertaking for any company, a UDI champion and implementation team should be created with members from all impacted departments before beginning the planning process. It is also important to involve top management because obtaining management support is critical to a successful implementation.

Step 3: Selecting an Issuing Agency

The next step of the UDI implementation process is to select an Issuing Agency that best meets your needs and your customers’ needs. The FDA accredited three organizations that assign Labeler IDs you can choose from: GS1, the Health Industry Business Communications Council (HIBCC), and the International Council for Commonality in Blood Banking Automation (ICCBBA). GS1 and HIBCC assign Labeler IDs to “labelers) of medical devices, while ICCBBA is for medical devices of human origin (blood, cell, tissue, and organ products), also known as HCT/P. GS1 assigns Global Location Numbers (GLN), HIBCC uses Health Industry Numbers (HIN), and ICCBBA issues Facility Identification Numbers (FIN).

If your company is not already partnered with one of the Issuing Agencies or still needs to select an Issuing Agency, you should survey your key customers to determine if they are implementing UDI systems or already have UDI systems. You may find customers using all three versions of UDI labeling (GTIN from GS1, HIBC from HIBCC, and ISBT-128 from ICCBBA). If you don’t label blood, cell, tissue, and organ (HCT/P) devices, then you can rule out ICCBBA. Conversely, if you only sell HCT/P devices, you can rule out GS1 and HIBCC. Ultimately, selecting an Issuing Agency is your company’s to make–and remember that you can enter two different Issuing Agencies for each medical device in the GUDID.

Step 4: Unique Device Identification Implementation Planning

Analyzing, strategizing, and planning are essential to determining if you will successfully implement UDI and the related GUDID submission. You need to fully understand your devices, labeling/manufacturing locations, and packaging requirements. Study the UDI Regulation to comprehend which aspects you must comply with as you develop your plan. Specifically, these undertakings should be completed as part of the planning process:

  • Start with the end in mind. Understand the UDI maze. What outcomes do you want?
  • Create a playbook to focus on solving business problems. Standardize procedures as much as possible and tailor solutions to your company’s needs.
  • Group your products by Device Class, Manufacturing Location, Packaging Requirements (sterile, kit, etc.), and any other criteria you need.
  • Perform a gap analysis between the device information you have and what you need for submission to GUDID.
  • Determine if your data management system(s) can maintain GUDID information and communicate UDI or DI information as required (sales orders, purchase orders, labeling, etc.).
  • Determine what changes need to be made to your existing quality system procedures.
  • Will revalidation of electronic records be required to comply with 21 CFR Part 11? (Note: Companies or third parties using HL7 SPL for data submission to GUDID will need to validate the software used for this purpose.)
  • Determine early on what additional resources are needed (FTE or consultants).

This information gathering should be used to create a strategic plan and budget. The plan should include timelines and assignments and identify strategic partners (outside vendors and customers). The plan should address changes required in your product lifecycle management (PLM), enterprise resource planning (ERP), supply chain systems, labeling/packaging equipment, and procedures. It should define the gateway to GUDID submission and create action plans for validation and compliance.

In my next blog post, I will discuss implementation and ongoing maintenance.

The First 4 Steps of Unique Device Identification Implementation Read More »

5 Common Mistakes Related to Compliance with FDA Recalls (21 CFR 806)

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FDA Recall 01 5 Common Mistakes Related to Compliance with FDA Recalls (21 CFR 806)This article identifies five common mistakes that occur when companies conduct FDA recalls, as required by 21 CFR 806.

As an experienced FDA medical device investigator, at one time or another, many firms I inspected struggled with deciphering FDA regulations and would misinterpret 21 CFR 806 (http://bit.ly/21CFR806-Recall). Fortunately, FDA 483 inspection observations can be easily avoided by doing two things. First, personnel responsible for corrections and removals need proper training—not just “read and understand.” Second, your forms and procedures need to comply fully with 21 CFR 806. The following is a list of 5 common mistakes made that are related to 21 CFR 806:

  1. incorrect interpretation of recall exemptions
  2. misinterpretation of reporting and documentation requirements
  3. failure to comply with recall reporting timelines
  4. failure to properly classify a recall
  5. insufficient recall training for quality personnel

21 CFR 806.1(b) – Recall Exemptions

The section of the regulations that deal with recall exemptions, 21 CFR 806.1(b), is the most widely confused interpretation. There are four categories of exemptions from correction and removal reporting:

  1. “actions were taken by device manufacturers or importers to improve the performance or quality of a device, but that does not reduce a risk to health posed by the device or remedy a violation of the act caused by the device.

  2. Market withdrawals as defined in 806.2(h).

  3. routine servicing as defined in 806.2(k), and

  4. stock recoveries as defined in 806.2(l).”

The risk to health is referenced in 21 CFR 806.1(b)(1) and has two definitions. The first is easily interpreted when there is a reasonable probability that the use or exposure of a medical device could cause serious adverse health consequences or death. Part 2 is confusing in that the definition states that a risk to health can be considered a temporary or medically reversible adverse health consequence, or the possibility of serious adverse health consequences is remote. The second part of the definition of “risk to health,” is not clarified in the recall regulations. Still, you can refer to 21 CFR 803.3 (Medical Device Reporting definitions) for the definition of “serious injury”:

  1. an injury or illness that is life-threatening,
  2. results in permanent impairment of a body function or permanent damage to a body structure, or
  3. necessitates medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure.

21 CFR 806.10 – Reporting & Documenting FDA Recalls

This section, 21 CFR 806.10 (http://bit.ly/Reporting-FDA-Recalls), is frequently misinterpreted. Corrections and removals by manufacturers and importers require reporting to CDRH, but there are two conditions. Either of the following conditions requires reporting if the correction or removal was initiated:

  1. “To reduce a risk to health posed by the device; or.”
  2. “To remedy a violation of the act caused by the device which may present a risk to health unless the information has already been provided as outlined in paragraph (f) of this section or the corrective or removal action is exempt from the reporting requirements under 806.1(b).”

It is usually better to err on the side of caution and report the correction and removal, but in all cases, properly document your rationale for reporting or not reporting.

21 CFR 806.10(b) – Recall Timelines

Reporting of corrections and removals requires the firm to report these recalls to FDA within ten days. Timeframes are important, so the information can be disseminated to the Regional and District Office after notifications are made to the FDA. 

21 CFR 7.3(m) – Recall Classification

Even when manufacturers and importers file a recall report within the specified timeframes, many times, the recall is improperly classified. Many manufacturers fail to classify their correction and removal based on severity properly. As reported by the FDA in 2013, a study (http://bit.ly/CDRH-Recall-Report) was conducted by CDRH on reported recalls, and this explanation of recall classifications was provided:

“As defined at Title 21, Code of Federal Regulations (CFR), 7.3(g), ‘Recall means a firm’s removal or correction of a marketed product that the Food and Drug Administration considers being in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure.’

  • A Class I recall is a situation in which there is a reasonable probability that the use of or exposure to a violative product will cause serious adverse health consequences or death.
  • A Class II recall is a situation in which the use of or exposure to a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.
  • Also, a Class III recall is a situation in which the use of, or exposure to, a violative product is not likely to cause adverse health consequences.”

Insufficient Training on FDA Recall Procedures

Each year, the FDA emphasizes the need for investigators to determine that each firm under the FDA area of jurisdiction properly maintains “Recall SOPs,” provides training on these procedures, and fully implements them. When your company performs an initial review of a recall procedure, or the recall procedure is re-written, a systematic review of each element in the regulations is needed. When you perform this review for your Recall SOP, ensure that you verify each of the first four common mistakes are addressed. You should also consider creating an exam to verify the effectiveness of training (http://bit.ly/TrainingExams). If your company manufactures or imports radiologic devices, ensure that the special requirement below is included in your procedure.

Special Requirement: Radiation Emitting Devices

Radiation emitting devices, such as medical lasers, X-Ray, and UV emitting devices, hold another special requirement seldom observed by the CDRH Compliance officers and FDA investigators that are not fully trained in radiation-emitting devices. If a medical device manufacturer or importer becomes aware of a defect in any radiation-emitting device that could cause serious injury, death, or require medical intervention to preclude serious injury or death, this defect must be reported to FDA under 21 CFR 1003. This regulation is one of the few FDA regulations that have significant teeth to mandate each manufacturer or importer to “Repair, Replace or Refund the purchase price” of the device when the manufacturer becomes aware of a major defect in their device (21 CFR 1004). This applies to medical and non-medical radiation-emitting devices, both of which are under FDA jurisdiction.

In some extreme cases, when I observed major defects in a medical device that also included a radiation-emitting device as well, if the CDRH Office of Compliance was unwilling to require a recall of the device, the recall could be mandated by the CDRH Division of Enforcement B (http://bit.ly/CDRH-Divisions-and-Offices). Division of Enforcement B has responsibility for enforcement of medical device regulations to radiologic devices.

Medical Device Academy recorded a webinar on the topic of FDA recalls. You can purchase the webinar by clicking on the following link: http://bit.ly/FDA-recalls-webinar.

5 Common Mistakes Related to Compliance with FDA Recalls (21 CFR 806) Read More »

UDI Costs: Long-Term Expenditures May Not Be Obvious

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jon money UDI Costs: Long Term Expenditures May Not Be Obvious Our author says to expect UDI costs to be as much as 1%+ of annual sales. Ongoing costs and post-market surveillance factors are also discussed. This new regulation is not without its costs. Some are significant, especially to small medical device labelers. There are the obvious implementation costs and ongoing maintenance. There are also “Post-market Surveillance Factors,” which may be a cost or benefit, but Post-Market Surveillance Factors certainly have long-term implications for your company.

UDI Costs to Industry

“The [UDI] final rule may have a significant economic impact on a substantial number of small entities that label medical devices.” (Federal Register – Cost and Benefits) Eastern Research Group, Inc. (ERG), under contract to FDA, “…estimated present value of the costs to domestic labelers is $620.4 million using a 7 percent discount rate and $713.2 million using a 3 percent rate…” over 10 years. Over the same time period, the annualized costs for domestic labelers are estimated to be $82.6 million at a 7 percent discount rate and $81.2 million at 3 percent. Medical device labelers will incur most of these costs. Labelers include manufacturers, reprocessors, specification developers, repackagers, and re-labelers that induce a label to be affixed to a medical device. ERG estimated costs would not eclipse 1% of revenues annually, except for a small percentage of companies required to mark specific devices directly. Some multi-use device manufacturers required to direct mark their Class I devices could benefit from reduced total costs if all of their device labels only need static barcodes, rather than more costly variable barcodes (DI +PI).  ERG also estimated 32 firms out of 5,234 domestic medical device labelers (5,010 are small businesses) will bear costs greater than 1% of revenues, due to needing costly laser direct marking equipment. Interestingly, all 32 firms are all considered small businesses.

Implementation Costs

Most of the costs associated with UDI are related to implementation. The following is a list of examples:

  • planning and integration of UDI throughout information systems
  • creation, review, and approval of labeling changes
  • digital printers to print the new barcodes and date formats
  • increased printing due to variable barcodes
  • joining issuing agency and obtaining labeler ID
  • requesting Global Medical Device Nomenclature (GMDN) Preferred Term (PT) codes
  • registering new barcodes
  • laser-etching of UDI barcodes on devices for direct marketing
  • compliance with the FDA’s UDI data uploading requirements
  • review and approval of procedure changes

The first item on the above list, planning, and integration, will be the highest cost of UDI implementation. The price of planning and integration includes installation, testing, and validation of barcode printing software. You will also need to retrain almost every department to understand how UDI is being integrated with existing processes. You may also need to temporarily increase your workforce to help ensure timely implementation to ensure compliance with the data attributes required for each device entered into the Global UDI Database (GUDID).

Ongoing Costs

The highest annual ongoing cost includes labor, operating, and maintenance associated with equipment for printing labels, and labor related to software maintenance and training needed to maintain the GUDID system. Other ongoing costs include paying initial and annual fees to the Issuing Agencies and/or the  GMDN agency (http://bit.ly/GMDN-Agency) for ongoing maintenance of the system. You will need to have additional personnel in most cases to manage these other requirements.

Post-market Surveillance Factors

Post-market Surveillance Factors are either a cost or benefit to the labeler, and are directly related to the Patient Safety and transparency aspects of the UDI Regulation. The goals of the FDA in enacting the UDI Regulation are:

  • reduce medical errors
  • simplify assimilation of device use information into database systems (such as Electronic Health Records and Personal Health Records)
  • provide for quicker identification of medical device adverse events; improve the speed of the development of solutions to reported problems
  • hasten and improve the efficient closure of device recalls
  • more focused and effective FDA Safety Communications
  • allow professionals and end-users access to additional product information via GUDID

In my opinion, there are other factors just as important which companies should pay attention to as they complete UDI requirements, including the ability to:

  • develop complete safety and effectiveness profiles for devices
  • reduce waste by helping to eliminate duplicate inventory at healthcare facilities
  • identify new uses for devices, which will help increase value for shareholders, customers, and end-users

Today, the identity of labelers is hidden from users and patients. Tomorrow, when the FDA’s goals are realized, labelers will be faced with increased transparency. You will need to address increased transparency by acting quickly to product performance trends. In today’s world of instant communication, you cannot afford to ignore safety issues brought to light by post-market surveillance factors. Anyone who does does so at their peril.

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What is the GUDID?

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This blog, “What is the GUDID?” reviews the basics of the database, do we need a GUDID account? How data is submitted, what information is needed, and more. 

What is the GUDID?

FDA, in creating the Unique Device Identifier (UDI), was looking to improve the postmarket surveillance process, which included developing a database to be used by the healthcare community and the public to obtain critical information on the medical devices they use. The Global UDI Database (GUDID – pronounced Good-I-D) is a repository for key device identification information. It will not include any patient information. This key information – 62 different data elements (see below) – is limited to Device Identifiers (DI) and Labeler information. Every Labeler of medical devices is required to have a UDI and submit this information to the GUDID.

Changes from the proposed rule impacting GUDID

In the proposed rule, FDA did not want to use Global Medical Device Nomenclature (GMDN) Preferred Term (PT) codes. Unfortunately, the GMDN PT codes are not free, and a subscription is required to access the GMDN Database. FDA was able to negotiate an agreement with the GMDN Agency to allow Labelers access to the GMDN PT codes. These codes will only be accessible to Labelers who enter device information using FDA’s Web Interface submission process. A word of caution; the GMDN Agency is continually adding and updating these codes. Companies submitting data via HL7 SPL (see below) will need to subscribe to the GMDN Agency to gain access to these codes.

what is GUDID What is the GUDID?

Another change deals with MRI compatibility. If you claim your device is MR Safe, MR Conditional, or MR Unsafe, then this information is now required as part of the submission to GUDID.

A new version of the GUDID Implementation Specification (Version 1.2.1, released April 11, 2014) is now available. FDA Global UDI Database Web Site 

Do we need a GUDID account?

To submit medical device key information, Labelers need to request an account through the FDA GUDID website. The Labeler Organization may have more than one GUDID account. A Duns and Bradstreet (DUNS) number for the company location is used to identify each GUDID account. The labeler must also be registered with the FDA as an establishment.

There are three (3) levels – Organization (which may also be a Labeler), Labeler, and Third-Party (entity authorized to submit GUDID information on behalf of Labeler). Each GUDID account must have:

  • One (1) Regulatory Contact
  • One (1) Coordinator (manages Labeler Data Entry users)
  • One (1) Labeler Data Entry user (day-to-day data entry)
  • One (1) Labeler DUNS number

Labeler DUNS number must match name and address on the device label.

Production Identifiers (PI) are not entered into the Database (just PI flags to indicate which PI are on the label). 

How data is submitted to GUDID

There are two standard-based methods to submit data: 1) structured input via a web interface, and 2) the Health Level 7 Structured Product Labeling (HL7 SPL) process. The first method, using a web-based interface, will work well for up to 200 total records. If you attempt to input more than 200 records, the input becomes overwhelming, and you will need to use the HL7 SPL process. HL7 SPL is in XML format and uses the FDA Electronic Submission Gateway (ESG) as the pathway to upload data into GUDID. Both submission methods are one DI record at a time. There is no batch option available.

You are also able to use third-parties to submit data. GS1 GDSN (Global Data Synchronization Network) is one example; there are others as well. Or you could build your submission tool.

There are three (3) states of entry –

  • Draft DI – only available via Web interface (Draft DI will be available for 180 days)
  • Unpublished – has passed all the business rules
  • Published – is now searchable

Currently, the GUDID search and retrieval options are not currently operational, as FDA is waiting until sufficient data has been entered to turn this feature on.

What information do I need?

There are 60-plus data attributes that need to be provided. Some of the fields are automatically filled in by the GUDID system, based on information that is entered. For instance, the Labeler Name and Address are pulled from the DUNS database, based on the DUNS number entered. An entry can have more than one Device Identifier. This is usually the case if you have used different Issuing Agencies. Attributes on label/package and the values submitted should match. GUDID also has controlled vocabulary and built-in business rules that will continually check what data is input.

A controlled vocabulary is DUNS #, GMDN code, and FDA Product Codes. 

Examples of Business Rules are:

  • All required data elements must be provided
  • Validating specific elements – FDA Listing #, etc.
  • Data constraints on specified elements – Publish date must always be >= TODAY
  • There are other additional business rules

Also, a DI can never be reused, even if it is discontinued. It will remain in GUDID, but marked as “Not in Commercial Distribution.”

What is the GUDID? Read More »

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