FDA Proposes New Rule for Acceptance of Data from Clinical Studies for Medical Devices

The Food and Drug Administration (FDA) is proposing to amend its regulations on acceptance of data from clinical studies for medical devices. The proposed regulation would require that clinical studies conducted outside the United States in support of an investigational device exemption (IDE) application, a premarket notification (510(k)) submission, a premarket approval (PMA) application, a product development protocol (PDP) application, or a humanitarian device exemption (HDE) application be conducted in accordance with good clinical practice (GCP), which includes obtaining and documenting the review and approval of the study by an independent ethics committee (IEC) and obtaining and documenting freely given informed  consent of study subjects.  The proposed rule is intended to update the standards for FDA acceptance of data from clinical studies conducted outside of the United States and to help ensure the protection of human subjects and the quality and integrity of data obtained from these studies.  As part of this proposed rule, FDA is also proposing to amend the IDE and 510(k) regulations to address the requirements for acceptance of data from clinical studies conducted inside the United States.  The proposed amendments are intended to provide consistency in FDA requirements for acceptance of clinical data, whatever the application or submission type.

http://www.gpo.gov/fdsys/pkg/FR-2013-02-25/pdf/2013-04201.pdf?source=govdelivery

FTC Online Ad Guidance - what will FDA do ?

Yesterday FTC has come up with a set of guidelines for online advertising aiming in particular,  to address the myriad questions surrounding the use of such tools as Twitter and Facebook to promote products and disseminate messages.
The key question is , FDA going to follow it, copy it if yes to what extent. The various questions which might restrict FDA from following is 

Would an advertiser be permitted to include, or embed, a hyperlink that allows a consumer to migrate from an ad to another web location that contains additional information? 
Drugmakers that want to use Twitter are confined by a 140-character Tweet, but what remains unclear is whether the FDA would allow a quick click on a link that takes consumers elsewhere to read safety information.

FTC says "disclosures that are an integral part of a claim or inseparable from it should not be communicated through a hyperlink. Instead, they should be placed on the same page and immediately next to the claim, and be sufficiently prominent so that the claim and the disclosure are read at the same time… This is particularly true for cost information and certain health and safety disclosures"

It has given many examples which can be found on the Document - How to Make Effective Disclosures in Digital Advertising

Now FDA has released RFP asking vendors to help in monitoring online ads 
http://complianceblog.blogspot.in/2013/03/fda-roles-out-rfp-doc-for-vendors-to.html

Related Training -

Social Media and Marketing FDA Regulated Products

Promoting and Advertising Dietary Supplements in Compliance with FDA and FTC Regulations: One and a Half-day In-person Seminar

Ensuring Compliance with Advertising and Promotional Requirements for Drugs and Medical Devices: 2-day In-person Seminar

Guidance on pulse oximeter applications

March 4 2013, The FDA issued new guidance governing premarket notification submissions for pulse oximeters. The new guidelines apply to all 510(k) submissions for the non-invasive blood oxygen level and pulse rate measuring devices.

In the guidance,  the FDA specified new rules for identifying, testing and assuring safety for the systems. The new document overrides the 1992 guidance on the same category. it will help device companies prepare their premarket notifications, or 510(k)s, for any pulse oximeter.

Scope 

The scope of this document is limited to the Class II devices, Oximeter and Ear oximeter, classified under the following regulations:

21 CFR 870.2700 – Oximeter (product codes: DQA (Oximeter) and NLF (Oximeter, Reprocessed))

An oximeter is a device used to transmit radiation at a known wavelength(s) through blood and to measure the blood oxygen saturation based on the amount of reflected or scattered radiation. It may be used alone or in conjunction with a fiberoptic oximeter catheter.Contains Nonbinding Recommendations

This guidance does not address oximeters in product codes MUD (tissue saturation oximeter), NMD (reprocessed tissue saturation oximeter), or MMA (fetal pulse oximeter).

21 CFR 870.2710 –Ear Oximeter (product code: DPZ (Ear oximeter))

An ear oximeter is an extravascular device used to transmit light at a known wavelength(s) through blood in the ear. The amount of reflected or scattered light as indicated by this device is used to measure the blood oxygen saturation.

Internal Control: Guidance to Directors” or Turnbull Guidance

The Turnbull guidance or the 'Internal Control: Guidance to Directors' sets out best practice on internal control for UK listed companies, and assists them in applying section C.2 of the UK Corporate Governance Code.
The guidance was originally published in 1999. In 2004 the FRC set up a group chaired by Douglas Flint (then Group Finance Director, HSBC Holdings plc) to review the guidance and update it where necessary, in the light of experience in implementing the guidance and developments in the UK and internationally since 1999.

How Can UK Companies Comply with the FRC “Internal Control: Guidance to Directors” or Turnbull Guidance? Best Practices to Follow

EBA Guidelines on Internal Governance

In the European Banking Authority's (EBA) new Guidelines on Internal Governance the aim is to enhance and consolidate supervisory expectations and improve the implementation of internal governance arrangements for individual institutions and the banking system as a whole

It has 6 key sections .
1 -Corporate Structure and Organization
The management body should ensure that there is a suitable and transparent corporate structure. It should access how the different structures complement and interact with each other . The operational structure is inline with approved business strategy. If they are operating in a special structure not falling under jurisdiction of international banking regulations, the management body should understand the particular risk associated with  it.

2- Management Body

• it should have overall responsibility and it should be clear and written in documents which in turn should have been approved.
• management should conduct an annual review of the effectiveness of internal governance framework and implementation.
• management body should have written policy for managing conflicts
• members should be engaged actively in business of the institution and should be able to make their own sound,objective and  independent decisions.
• management body should consider setting up various committee with members as part of the committee keeping in to account of the size and complexity of the institution ex- audit committee, remuneration,ethics and compliance committee.

What is FINRA and the guidances

FINRA is Financial Industry Regulatory Authority, Inc., is a private corporation that acts as a self-regulatory organization (SRO) and established in June 2007 . It is the successor to the National Association of Securities Dealers, Inc. (NASD).
FINRA’s mission is to protect America’s investors by making sure the securities industry operates fairly and honestly.

Various guidance by FINRA

•Standards of Commercial Honor and Principles of Trade (FINRA Rule 2010)
•Communications with the Public (NASD Rule 2210)
•Guidelines to Ensure Communications With the Public are Not Misleading (IM- 2210-1)
•Recordkeeping (NASD Rule 2210(b), NASD Rule 3110 and SEC Rule 17a-4)
•Approval and Supervision (NASD Rules 2210(b) and 3010)
•Suitability: Recommendations to Customers (NASD Rule 2310) and Online Communications (Regulatory Notice 01-23)
•Conflicts of Interest (NASD Rule 2711, IM-2210-1 (6)(C) and Regulatory Notices 07-04, 04-18 and 03-44)
•Day Trading Rules (Rules 2270 and 2130)

Guidance document on the management of design and process changes

To ensure that good quality assurance practices are used for the design of medical devices and that they are consistent with quality system requirements worldwide, the Food and Drug Administration revised the Current Good Manufacturing Practice (CGMP) requirements by incorporating them into the Quality System Regulation, 21 CFR Part 820. An important component of the revision is the addition of design controls.
Because design controls must apply to a wide variety of devices, the regulation does not prescribe the practices that must be used. Instead, it establishes a framework that manufacturers must use when developing and implementing design controls. The framework provides manufacturers with the flexibility needed to develop design controls that both comply with the regulation and are most appropriate for their own design and development processes.
This guidance is intended to assist manufacturers in understanding the intent of the regulation. Design controls are based upon quality assurance and engineering principles. This guidance complements the regulation by describing its intent from a technical perspective using practical terms and examples.
You can download the guidance here - Design Control Guidance For Medical Device Manufacturers

In the last GHTF STEERING COMMITTEE MEETING last October a discussion started regarding the potential need for a guidance document on the management of design and process changes . It was decided that there is no consolidated approach to how changes are assessed by the regulatory jurisdictions. Hence in coming days the user group 1 of the GHTF is assigned to create the guidance document.

Compliance with the New Draft Guidance on Process Validation

FDA have released a draft Guidance document titled "Guidance for Industry - Process Validation: General Principles and Practices .The following categories of drugs are within the scope of this guidance: Human drugs Veterinary drugs Biological and biotechnology products Finished products and active pharmaceutical ingredients (API or drug substance)The drug constituent of a combination (drug and medical device) product The following categories of products are not covered by this guidance: Type A medicated articles and medicated feed Medical devices Dietary supplements Human tissues intended for transplantation regulated under section 361 of the Public Health

The draft guidance can be found at http://www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0559-gdl.pdf

Article - FDA's New Process Validation Guidance Recommends Team Approach

http://www.thephantomwriters.com/free_content/db/h/fda-process-validation-guidance.shtml

Webinar on this topic - http://www.ispe.org/cs/webcasts/process_validation

Reportable Food Registry Draft Guidance

The RFR is scheduled for implementation on September 8, 2009, and applies to all FDA-regulated categories of foods, including dietary supplements. Only infant formula is exempt from the RFR requirements.

The RFR requires a responsible party to file a report through an FDA internet portal when there is reason to believe that an adulterated food (other than infant formula) will cause serious adverse health consequences or death to humans or animals. "Responsible party" is defined as the person who submits the registration information to FDA for a food facility that manufactures, processes, packs, or holds food for human or animal consumption in the United States. Federal, state, and local government officials may also use the portal to report information that may come to them about such foods.

Submit electronic comments on the draft guidance to http://www.regulations.gov/.

Find out what are its implecations and loopholes click the link below

http://www.kelleydrye.com/resource_center/client_advisories/0475

Elements of Obama's healthcare reform plan

Obama expects to see a healthcare bill by end of 2009. The most important factor is to be discussed is increased insurance access for the under and uninsured.Reports from wasignton D. C suggest that a serious effort will be under way through out the summer to craft bill and get it to the President's desk for signature before end of the year.
I found a good report on these developments from Pharmavoice.
click on the link to read the full article

CGMP guidance for Phase I Investigational Drugs

This guidance got approved in July , 2008

This Replaces guidance issued in 1991 “Preparation of Investigational New Drug Products for the manufacture of phase I investigational drugs” . However the 1991 guidance still applies to the manufacture of investigational new drugs(human and animal) used in phase II and phase III clinical trials
This guideline is intended to help in applying current good manufacturing practice (CGMP) required under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in the manufacture of most investigational new drugs (IND) used in phase I clinical trials.

This guidance describes an approach to
•Implementation of manufacturing controls that are appropriate for phase I clinical trial stage of development
•Product quality differences
−Between investigational drugs and commercial manufacture
–Among the various phases of clinical trials
•FDA's CGMP for the 21 Century initiative
– Where applicable, manufacturers are also expected to implement manufacturing controls that reflect product and manufacturing considerations, evolving process and product knowledge, and manufacturing experience .
Scope

This guidance applies to phase I investigational drugs for human use that are
•manufactured in small or large-scale environments
•typically designed to assess tolerability, or feasibility, for further development of a specific drug or biological product
•new drug and biological products including finished dosage forms used as placebos

- Investigational drugs used in phase I studies described in 21 C.F.R. § 312.21 of FDA’s IND regulations are EXEMPTED from the Current Good Manufacturing Practice (“CGMP”) requirements in 21 C.F.R. Part 211
- This exemption does not apply to an investigational drug for use in a phase I study once the investigational drug has been made available for use by or for the sponsor in a phase II or phase III study, or the drug has been lawfully marketed
- The exempted phase I drugs are, however, still required to meet statutory (as opposed to regulatory) requirements for CGMP

This guidance DOES NOT apply to phase I investigational drugs for human use that are
−Human cell or tissue products regulated solely under § 361 of the Public Health Service Act
−Clinical trials for products subject to the device approval or clearance provisions of the FD&C Act
−Investigational products manufactured for phase II and phase III clinical trials
−Previously approved products that are being used in phase I clinical trials (e.g. for a new indication)
−Positron Emission Topography (PET) drugs that are subject to § 501(a)(2)(C) of the FD&C Act and/or the new PET CGMP in 21 CFR part 212 when finalized

FDA Guidance on Computerized Systems Used in Clinical Investigations

Scope of this guidance

Computerized systems that contain data that support a marketing application
–Case histories
–Analytical test results (e.g., LIMS)
–Data captured from analytical instruments
–Electronic transcription of hardcopy source data
it Does not apply to:
–Computerized medical devices

Study Protocols
•Identify computerized system use within the trial process
•Computerized systems must:
–Satisfy process requirements defined in study protocol
–Have built-in error prevention

•Challenges
–More complicated protocols
–Some automated processes may not be defined at protocol authoring stage – Unnecessary protocol revisions

SOPs and system documentations

•Specific to computerized system
–Setup/Installation instructions
–Operating manual
–Validation
–Data collection and handling
–System maintenance
–Security controls
–Change control
–Backup/Restore
–Disaster recovery/contingency planning
–Data collection contingencies
–Training
–Roles and responsibilities

•Challenges
–Guidance states “Such SOPs should be maintained either on-site or be remotely accessible through electronic files as part of the specific study records, and the SOPs should be made available for use by personnel and for inspection by FDA.”

Source Documentation and Retention
•Original observations entered directly in computer = source document
•Investigator must retain source data, or a copy
•If source data not generated and stored at clinical site, a copy must be provided to clinical site or a designated site
–Copies must be made contemporaneously with data entry

•Challenges
–Does contemporaneous mean simultaneous?
•Initial impressions from FDA = Yes
•Often not logical and sometimes demonstrably impossible
•CDISC eSDI guidance on Electronic Source Data within Clinical Trials: “as soon as possible after the event to which it refers
–FDA’s concern: If Investigator does not retain a copy of the source data, the records can be modified and original data obscured
–Although Investigator may be able to remotely access data at Sponsor site, it is not under his/her control
–No longer acceptable to just send investigator copy of data at end of study

Access control

–Individual accounts
–Limit log-in attempts and record failed attempts
–Work only under own password/account
–Do not share password
–Password aging
–Procedural or automatic log-offs or lock-outs
–The system should not allow an individual to log onto the system to provide another person access to the system*

•Challenges
–“The system should not allow an individual to log onto the system to provide another person access to the system”
–How does the system control this?
•Should you not allow concurrent logins?
•Should you require periodic user checkpoints in the system?
•Does “system” include both the computerized application and procedural controls?

FDA Guidance on Computerized Systems Used in Clinical Investigations

Scope
Computerized systems that contain data that support a marketing application

• Case histories
• Analytical test results (e.g., LIMS)
• Data captured from analytical instruments
• Electronic transcription of hardcopy source data

it Does not apply to Computerized medical devices*
Study Protocols
•Identify computerized system use within the trial process
•Computerized systems must:
–Satisfy process requirements defined in study protocol
–Have built-in error prevention
•Challenges
–More complicated protocols
–Some automated processes may not be defined at protocol authoring stage – unnecessary protocol revisions
•Potential Solutions
–Include only high level detail in study protocol
–Maintain detailed computerized process map outside study protocol
SOPs and System Documentation

•Specific to computerized system
–Setup/Installation instructions
–Operating manual
–Validation
–Data collection and handling
–System maintenance
–Security controls
–Change control
–Backup/Restore
–Disaster recovery/contingency planning
–Data collection contingencies
–Training
–Roles and responsibilities

•Challenges
–Guidance states “Such SOPs should be maintained either on-site or be remotely accessible through electronic files as part of the specific study records, and the SOPs should be made available for use by personnel and for inspection by FDA.”
•Potential Solutions
–Considerations for which SOPs are implemented at the site
For detailed description on this topic please attend the training
http://www.complianceonline.com/ecommerce/control/trainingFocus/~product_id=700842&channel=blog

What are the guidance documents that govern MDDs?(Microbial Data Deviation Investigations)

Regulatory and Guidance Documents
•2006 FDA Guidance for Industry - Investigating Out of Specification (OOS) Test Results for Pharmaceutical Production.
•ICH Q6A
•ICH Q7A
•USP 31 <1117> Best Microbiological Practice

•Addressed in PMF Newsletter (Sutton and Settineri)
http://www.microbiologyforum.org/PMFNews/PMFNews.12.11.0611.pdf (Sutton)
http://www.microbiologyforum.org/PMFNews/PMFNews.13.06.0706.pdf (Settineri)
•Addressed in PDA Draft Technical Report
Points to Consider When Investigating Microbiological Data Deviations (MDD) (Formerly known as the Micro OOS Task Force)

•Tangentially addressed in FDA Aseptic Processing Guidance albeit it is focused on sterile products. http://www.fda.gov/cber/gdlns/steraseptic.pdf