Tag Archives: medical device

Medical Device Safety and Recalls: FDA Recommends Health Care Facilities Transition from Custom Ultrasonics Endoscope Washer/Disinfectors to Alternate Reprocessing Methods: FDA Safety Communication

Medical Device Safety and Recalls: FDA Recommends Health Care Facilities Transition from Custom Ultrasonics Endoscope Washer/Disinfectors to Alternate Reprocessing Methods: FDA Safety Communication

Today, the FDA issued the Safety Communication, “FDA Recommends Health Care Facilities Transition from Custom Ultrasonics Endoscope Washer/Disinfectors to Alternate Reprocessing Methods
to notify health care professionals about our concerns with the safety and effectiveness of all Custom Ultrasonics’ AER models. This communication provides recommended actions health care facilities should take if they use Custom Ultrasonics’ AERs because of the risk of transmission of infectious organisms to patients.

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Medical Device Single Audit Program (MDSAP) Mid-Pilot Status

The FDA just released the Mid-Pilot Report for the Medical Device Single Audit Program (MDSAP), to provide the current status of the program’s performance goal and objectives.

The goal of the MDSAP pilot is to provide objective evidence that a regulatory audit of a medical device manufacturer conducted by an MDSAP-recognized auditing organization can fulfill the needs of participating regulatory authorities.  The MDSAP pilot’s objectives include developing the infrastructure, processes, training, and stakeholder commitment necessary to launch the operational phase of the MDSAP in January 2017.

The participating regulatory authorities are the Therapeutic Goods Administration of Australia, Brazil’s Agência Nacional de Vigilância Sanitária, Health Canada, Japan’s Ministry of Health, Labour and Welfare, with the Japanese Pharmaceuticals and Medical Devices Agency, and the United States Food and Drug Administration.  The World Health Organization (WHO) Prequalification of In Vitro Diagnostics (IVDs) Programme and the European Union (EU) are official observers.

In a related matter, the new version of ISO 13485 Quality Management System standard, an important element on which the MDSAP Pilot is based, will publish in the coming months.  Two years after the ISO 13485 standard is published, third party auditing organizations or “registrars” may issue industry certifications only to the new version of the standard.

The FDA encourages manufacturers to participate in the MDSAP Pilot prior to the implementation of this key transition initiative, and before the program becomes mandatory in certain regulatory jurisdictions.

For more information about the MDSAP and the participating regulatory authorities, see the FDA’s MDSAP webpage.

Thank you,

Food and Drug Administration
Center for Devices and Radiological Health

Medical Device Safety and Recalls: Serious Adverse Events with Implantable Left Ventricular Assist Devices (LVADs

Today the FDA issued a safety communication regarding serious adverse events with Implantable Left Ventricular Assist Devices (LVADs). To date, there are two implantable LVADs approved by the FDA: The HeartMate II Left Ventricular Assist System manufactured by Thoratec Corporation, and the HeartWare Ventricular Assist System HVAD manufactured by HeartWare, Inc.

The FDA is aware of serious adverse events associated with both devices, and is alerting health care providers, patients, and caregivers about serious adverse events associated with LVADs. These adverse events include an increased rate of pump thrombosis (blood clots inside the pump) with Thoratec’s HeartMate II and a high rate of stroke with the HeartWare HVAD since approval of the devices. We are also aware of bleeding complications associated with both devices.

For more information, please see: http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm457327.htm

Disclaimer: The EDC Developer blog is “one man’s opinion”. Anything that is said on the report is either opinion, criticism, information or commentary, If making any type of investment or legal decision it would be wise to contact or consult a professional before making that decision

Medical Device Safety and Recalls: MicroPort Orthopedics Inc., PROFEMUR Neck Varus/Valgus CoCr 8 Degree, Part number PHAC 1254

Medical Device Safety and Recalls: MicroPort Orthopedics Inc., PROFEMUR Neck Varus/Valgus CoCr 8 Degree, Part number PHAC 1254

A recall has been issued for MicroPort Orthopedics Inc., PROFEMUR Neck Varus/Valgus CoCr 8 Degree, Part number PHAC 1254
. MicroPort Orthopedics Inc. has received reports of an unexpected rate of fractures after surgery related to this specific modular neck. If the modular neck fractures, the patient may experience sudden pain, instability and difficulty walking and performing common task. An acute fracture will require revision surgery to remove and replace the neck and stem components. Acute fracture and emergency revision surgery is a serious adverse health consequence and could lead to neurovascular damage, hematoma, hemorrhage, and even death.

CDISC Will Be Required by Kit Howard

Over the past decade or so, a tremendous amount of development work has gone into creating standards for data to be submitted electronically to the FDA. There are those, however, who question whether these standards will ever be required, and believe that unless the FDA requires them, the standards don’t have to be adopted. Indeed, in the absence of such a requirement, there is sometimes a good business case for not adopting the standards, for example, if the company already has their own robust standards, or when the exit strategy is to achieve proof of concept and then sell. The writing is on the wall, however. Standards will be required, at least for data submitted to FDA, and that includes CDER (drugs), CBER (biologics) and CDRH (devices). This article will present evidence of that, and cover sources for the agency’s expectations.

In February 2012, FDA issued a Notice of Proposed Rule Making called Electronic Submission of Data From Studies Evaluating Human Drugs and Biologics. This Notice outlined the FDA’s intention to require that all data submitted in support of clinical trials would have to be sent in “an electronic format that FDA can process, review, and archive.” This will cover new drug applications (NDAs, usually submitted to CDER), biologic license applications (BLAs, usually submitted to CBER and sometimes jointly to CDRH), and abbreviated NDAs (ANDAs, usually submitted to CDER and CBER, and sometimes jointly to CDRH), and all of the associated supplements and amendments. Later in the Notice, it states that “FDA’s proposed rule would address the submission of study data in a standardized electronic format.” While CDISC is not specifically mentioned, it is referenced in several other FDA documents.

There isn’t currently a rule specifically mentioning CDRH requiring standards, but there is a very strong commitment internally to adopting CDISC, so the probability is good that there will eventually be some kind of regulatory requirement.

Guidance
Providing Regulatory Submissions in Electronic Format — Standardized Study Data http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/ Guidances/UCM292334.pdf

FDA is issuing a series of guidances designed to help sponsors submit data electronically, and the most recent is a draft guidance titled Providing Regulatory Submissions in Electronic Format — Standardized Study Data. Its primary purpose is to state that data submitted to the agency must be submitted electronically and in a standardized structure. The draft was issued in February, and the comments period closed on April 23.

The guidance covers a much wider set of submissions than the proposed rule, including both clinical and nonclinical data submitted in investigational new drug applications (INDs), NDAs, ANDAs and BLAs, and also medical device data in investigational device exemptions (IDEs), pre‐ marketing notifications (510(k)s), and premarketing approval applications (PMAs). It also includes all supplements and amendments. It effectively means that all clinical and nonclinical data going to CDER, CBER and CDRH are covered.

The guidance describes the kinds of data the agency receives and why it will require that the data be standardized. The reasons are much as you’d expect ‐ they can receive, import, analyze and report on the data much more efficiently and spend much less time working out what data are where. The guidance then goes on to discuss processes for data that were captured in a standardized format and those that weren’t.

It is important to note that the guidance does not state that CDISC standards must be used, but rather says that standards must be used, and to see the FDA’s standards page for the specific standards that are currently required. This permits changes to the standards to happen without having to update the guidance. Most of the data‐specific examples use CDISC, and the strong hint is that this is what should be used.

Here are some key points:

  • The guidance clearly states that collecting data in the same standardized format in which they will be submitted is preferable to converting after collection, a practice that is discouraged.
  • For both clinical and nonclinical studies, the sponsor should outline their standards plan in the IND or IDE. This means that the standards strategy must be established before the clinical program starts. This has implications for companies that currently expect to do only a few studies and license the product out ‐ we should expect to see conformance to standards become a part of the assessment of quality of study data.
  • When study data are submitted, the cover letter should include a description of the standards used. The guidance specifically states that it does not define what should be collected, just that everything that is collected should be submitted in a standardized fashion.
  • Each submission should contain a Reviewers’ Guide that orients the user to the structure and content of the datasets. There is no guidance currently available as to the desired content of the guide at this time.
  • Controlled terminologies must be used, and the submission must note what ones were used. The guidance discusses the value of such terminologies.
  • In cases where non‐standard data are mapped to the standards, any variable that cannot be fully or exactly mapped must be documented and explained. Data validation as per the guidance is the process of making sure that the data conform to the standards rules. It is one aspect of data quality. There are 2 types of validation rules ‐ technical validation rules (e.g., is the variable name correct) and business validation rules (do the data make sense, e.g., is the heart rate compatible with life?).
  • The guidance notes that different parts of the FDA are adopting standards at different rates, and there‐ fore there may be exceptions to the requirements. Sponsors can request meetings with the review division to determine what the requirements will be for their studies/submissions.

Online Resources for FDA’s Standards Expectations

The FDA is developing a robust set of online resources to help organizations understand and adopt standards in the way that is most useful for all parties involved. Most can be found via the primary data standards page, which is FDA Resources for Data Standards, http://www.fda.gov/ForIndustry/DataStandards/ default.htm, and can be accessed from the main FDA page by clicking on For Industry, and scrolling down to the For Industry Topics to Data Standards. Note that the FDA websites are reorganized periodically, so this may change in time. Among other things, this includes links to the pages for the Structured Product Labeling and Individual Case Safety Report (terminology below), the Study Data Standards page (discussed below), and a link to the FDA’s Data Council, which has overall responsibility for FDA standards. Be aware that there are no links back to the Data Standards page from any of the linked pages, which is rather annoying.

This part of this article lists and describes some of the resources that are available on this page a number of them that may be of particular use.

The Study Data Standards page has the largest number of standards resources. Its url is: http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/default.htm. Here are some of the resources you can find there.

Study Data Specifications: a highly technical description of the software format the datasets should use (SAS XPORT), the file naming conventions, conventions for splitting large files, the format for the data tabulations (CDISC SDTM (human trials) or SEND (animal trials)), and the structure for data listings and patients profiles (this is quite limited). While CDISC ADaM is not specified, there are a number of rules for structuring the analysis datasets, including the need to provide both text and numeric versions of coded variables, and dates should be numeric rather than ISO8601. A define.xml is required that describes the dataset structures, an annotated CRF must be included, and a folder structure for the files is defined.

Study Data File Format Standards: a list of the file for‐ mats and what can be used to send what to whom (e.g., send study datasets to CDER, CBER and CDRH using SAS XPORT, send SDTM and ADaM define.xml to CBER and CDER using XML v1.0)

Study Data Exchange and Analysis Standards: speci‐ fies SDTM versions 1.1 and 1.2, the SDTM IG v3.1.1 and 3.1.2, SEND IG v3.0, and ADaM v2.1.

Study Data Terminology Standards: these are the code lists and dictionaries that should be used, including CDISC Terminology v 2011‐06‐10 or later, MedDRA v8 or later, CDRH Device Problem codes, and others.

Study Data Validation Rules: this is a list of rules to which submission data must conform, or it will be rejected by the agency’s data uploader.
There are also center‐specific pages that may be useful.

CBER: http://www.fda.gov/BiologicsBloodVaccines/ DevelopmentApprovalProcess/ucm209137.htm. This page has a very specific list of the steps you need to take to be ready to submit data to CBER in electronic format. It is critical that sponsors review and follow this list, as it is the first thing that the CBER contact (Amy Malla) will ask you. CBER started accepting CDISC‐formatted data in December 2010.

CDER: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ ucm248635.htm. The webpage starts with the following statement:

CDER strongly encourages IND sponsors and NDA applicants to consider the implementation and use of data standards for the submission of applications. Such implementation should occur as early as possible in the product development lifecycle, so that data standards are accounted for in the design, conduct, and analysis of studies.

It can’t get much blunter than that. It then references the Study Data Specifications document discussed above, the CDISC SDTM, SEND and ADaM, and includes a list of Data Standards Common Issues that lists the problems that CDER most commonly sees with respect to the standardization of submissions. Sponsors can use this to ensure they do not commit these errors. This document also suggests that CDASH‐style CRFs are best for simplifying the process of creating SDTM domains.

CDER began accepting CDISC‐formatted data some number of years ago.

  • CDRH: there isn’t a standards‐specific page for CDRH but they started accepting CDISC‐formatted data in May 2011. The same person (Amy Malla) is the contact for submitting data electronically to CDRH, and the list of steps on the CBER page is intended for use for CDRH data as well. CDRH has some standards terminologies defined that sponsors are ex‐ pected to use.

Some other resources that may be helpful are as follows.

  • A consolidated list of guidances (both draft and final) relating to electronic submissions http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064994.htm
  • FDA terminology hosted by the National Cancer Institute’s Enterprise Vocabulary Services (the same organization that hosts CDISC’s controlled terms) http://www.cancer.gov/cancertopics/cancerlibrary/ terminologyresources/fda
  • Structured product labeling terms, in‐ cluding Mechanism of Action, Physiologic Effect, Structural Class and Problem List Subset
  • Unique Ingredient Identifier (UNII)
  • Individual Case Safety Report
  • CDRH’s terminology, including Event Problem Codes that cover Patient Prob‐ lem Codes, Device Component Codes and Device Problem Codes. Note that these are listed with the link of Center for Devices and Radiological Health, rather than by the name of the code lists.

For the sake of completeness, here are the links for the CDISC standards

These are currently available resources, but of course this will grow as the agency develops more.

Kit Howard is a Clinical Data Standards, Quality and Management consultant for Kestrel Consultants.

Reference: The Proposed Rule

Disclaimer: The legal entity on this blog is registered as Doing Business As (DBA) – Trade Name – Fictitious Name – Assumed Name as “GAMBOA”.

Overview of the 510(k) medical device approval process in the USA

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