Simple steps to check back pain at work place

We all sit in single position for the whole day in the office, and ride the car, bike or use other means to reach our places. As a result at night, while going to bed, many of us experience a slight pain in the back.  Pay attention...or it may lead to many further diseases and disabilities as well....  Don't be panic, just do the following exercise for 10 mins every morning and shoot off the back pain.  Enjoy a healthy living....  Simple Exercises... to keep you fit and avoid back pain. Need not visit a gym, your home  or office may be the ideal place.

Series 4: Drug Development requirements through the eyes of FDA

Drug tests  on Humans or Clinical Studies

Clinical trials, also known as clinical studies, test potential treatments in human volunteers to see whether they should be approved for wider use in the general population. A treatment could be a drug, medical device, or biologic, such as a vaccine, blood product, or gene therapy. Potential treatments, however, must be studied in laboratory animals first to determine potential toxicity before they can be tried in people. Treatments having acceptable safety profiles and showing the most promise are then moved into clinical trials.

Although "new" may imply "better," it is not known whether the potential medical treatment offers benefit to patients until clinical research on that treatment is complete. Clinical trials are an integral part of new product discovery and development and are required by the Food and Drug Administration before a new product can be brought to the market.

The FDA is committed to protecting the participants of clinical trials, as well as providing reliable information to those interested in participating. Recently, unethical behavior on the part of some researchers has shaken the public trust and prompted the federal government to establish regulations and guidelines for clinical research to protect participants from unreasonable risks.

Although efforts are made to control risks to clinical trial participants, some risk may be unavoidable because of the uncertainty inherent in clinical research involving new medical products. It's important, therefore, that people make their decision to participate in a clinical trial only after they have a full understanding of the entire process and the risks that may be involved.

Forms & Submission Requirements

Investigational New Drug Forms (IND)

·        FDA 1571 (pdf)  Investigational New Drug Application ·        FDA 1572 (pdf)  Statement of Investigator ·        Instructions for completing FDA forms 1571 and 1572 ·        FDA Form Distributions Page. includes links to: Certification: Financial Interest and Arrangements of Clinical Investigators Disclosure: Financial Interest and Arrangements of Clinical Investigators MedWatch: FDA Medical Product Reporting Program - Voluntary MedWatch: FDA Medical Products Reporting Program - Mandatory ·        For electronic form submissions, see Electronic Regulatory Submissions and Review.

New Drug Application Forms (NDA)

·        Form FDA-356h (pdf) Application to Market a New Drug, Biologic, or An Antibiotic Drug For Human Use ·        Form FDA-3397 (pdf) User Fee Cover Sheet ·        Form FDA-3331 (pdf) New Drug Application Field Report

Abbreviated New Drug Application Forms (ANDA) for Generic Drug Products

·        Form FDA-356h (pdf) Application to Market a New Drug, Biologic or An Antibiotic Drug For Human Use ·        Guidance for Industry: Providing Regulatory Submissions in Electronic Format - General Considerations.

Orphan Drug Products (for rare diseases and disorders)

·        There is no form, but there is a prescribed format for application for orphan drug status. The section from the regulations that describes the format can be found on this website on the The Orphan Drug Act and Related Law and Regulations page.

Electronic Regulatory Submission and Review (ERSR)

·        Regulations and Instructions for Submitting Drug Applications Electronically.  This webpage provides for information on CDER's program to enable the electronic submission of regulatory information to the Center and the review of it by CDER staff.

Guidelines for Waiver Requests

Guidelines for requesting waiver to current supported clinical study data standard versions.  This webpage provides information on submission of data that does not conform to currently supported standard versions.

Code of Federal Regulations for Investigational New Drugs (INDs), New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs) and Biologics License Applications (BLAs)
The following Code of Federal Regulations(CFR) sections provide regulations for INDs, NDAs and BLAs.  All parts of section 21 of the Code of Federal Regulations are also available.

·        CFR Sections for INDs

·        CFR Sections for NDAs 

·        CFR Sections for ANDAs

·        CFR Sections for BLAs

    Part 600-Biological Products: General

    Part 601-Licensing

    Part 610-General Biological Products Standards  

  
Manual of Policies and Procedures (MaPPs) 
MaPPs provide official instructions for internal practices and procedures followed by Center for Drug Evaluation and Research (CDER) staff to help standardize the IND and NDA review process. All CDER MaPPs are available from the MaPP Index web page.

Series 3: Drug Development requirements through the eyes of FDA

Relevance of Office of Prescription Drug Promotion (OPDP)
OPDP formerly known as Division of Drug Marketing, Advertising and Communications - DDMAC. OPDP reviewers have responsibility for reviewing prescription drug advertising and promotional labeling to ensure that the information contained in these promotional materials is not false or misleading. They engage in a variety of tasks to perform this responsibility, including: providing written comments to pharmaceutical sponsors on proposed promotional materials to ensure clear and unambiguous communication of the laws and regulations relating to prescription drug promotion; reviewing complaints about alleged promotional violations; initiating enforcement actions on promotional materials that are false or misleading; comparing the product labeling and promotional materials of various closely related products to ensure that the regulatory requirements are consistently and equitably applied; traveling to major medical meetings and pharmaceutical conventions to monitor promotional exhibits and activities; and acting as a liaison between OPDP and other divisions within the FDA on promotional issues.
Important Information About Submissions

OPDP reminds all companies who are engaging in DTC advertising of prescription drugs that the requirements of section 906 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) went into effect on March 25, 2008.  Section 906 of FDAAA mandates that published direct-to-consumer advertisements for prescription drugs include the following statement printed in conspicuous text:  "You are encouraged to report negative side effects of prescription drugs to the FDA.  Visit www.fda.gov/medwatch for more information.

What are the general requirements for prescription drug advertisements directed toward consumers?

The same statute and regulations apply regardless of the audience targeted by a prescription drug advertisement. The Federal Food, Drug, and Cosmetic Act (the act) requires that all drug advertisements contain (among other things) information in brief summary relating to side effects, contraindications, and effectiveness. Because of this statutory wording, this requirement has become known as the brief summary.  The current advertising regulations specify that this information disclosure needs to include all the risk information in a products approved labeling. Typically, print advertisements will include a reprinting of the risk-related sections of the product's approved labeling (also called full prescribing information or the package insert). Sponsors, however, can write this risk information in language appropriate for the targeted audience; FDA encourages this approach.

In addition to the specific disclosure requirements, advertisements cannot be false or misleading or omit material facts. They also must present a fair balance between effectiveness and risk information. FDA has consistently required that appropriate communication of effectiveness information includes any significant limitations to product use.

How do prescription drug broadcast advertisements differ from print advertisements?

Current regulations specify two requirements that all prescription drug broadcast advertisements must meet. First, broadcast advertisements must include the product's most important risk-related information in the audio or audio and visual parts of the advertisement. This is sometimes called the major statement.  This requirement is not addressed by the guidance. Second, broadcast advertisements must contain either a brief summary of the advertised product's risk information, or alternatively, make adequate provision for disseminating the product's approved labeling in connection with the ad. Thus, the regulations for broadcast advertisements recognize broadcast's inherent limitations by providing an alternative mechanism for meeting the act's information disclosure requirement.

What needs to be included as part of the major statement requirement?

The major statement must include all of the most important risk information related to the product. Because risks vary from product to product, the amount of information disclosed for any particular product to meet this requirement will vary as well.

How does a product's brief summary differ from its approved labeling?

The brief summary is generally shorter -- sometimes significantly so. The brief summary typically includes only the risk-related sections of the product's labeling. This is because the advertising text itself generally meets the requirement for including effectiveness information by giving the product's indication (i.e., what it is used for), and any limitations concerning how and when the product should be used. In contrast, product labeling includes non-risk-related information, including all effectiveness information (sometimes even about the clinical studies used as the basis for product approval), how it should be taken (dosage information), how the drug product is supplied (e.g., the quantity of drug in each pill), and information about how the product works in people's bodies.

Does FDA intend to do anything about the brief summary information?

FDA has also heard concerns about the lack of value of the required information from some individuals and groups. It has heard from others that consumers should get full disclosure of risk information. The agency intends to address these concerns fully through the rulemaking process. In the interim, the agency encourages product sponsors to provide consumers with non-promotional, consumer-friendly information consistent with product labeling, along with the information required by the act and the regulations.   As mentioned above, in the case of print advertisements, FDA encourages sponsors to write their product brief summaries in consumer-friendly language.

May the phrase "drug of choice" be used in advertising or labeling?

The phrase "drug of choice," or any similar phrase or presentation, used in an advertisement or labeling would make a superiority claim and, therefore, the advertisement or labeling would require substantial evidence to support that claim.

Does the full prescribing information or the brief summary type have to be any particular size?

No, but the regulations specify size in sections 201.10(g)(2) and 202.1(b)(2) which state:
"The established name shall be in printed letters that are at least half as large as the letters comprising the proprietary name or designation with which it is joined, and the established name shall have a prominence commensurate with the prominence with which such proprietary name or designation appears, taking into account all pertinent factors, including typography, layout, contrast and other printing features."

Does "half as large" refer to point size or actual type size?

OPDP has interpreted "half as large" to be actual size, not point size, of upper and lower case letters in the proprietary and established drug names. 

May an advertisement or labeling piece include the phrase "FDA-approved"?

Yes, if the manufacturer or sponsor has received a letter stating that the product has been approved. Effective on the date of implementation, the Food and Drug Administration Modernization Act of 1997 eliminated Section 301(l) of the Federal Food, Drug, and Cosmetic Act that prohibited "The using . . . of any representation or suggestion that approval of an application with respect to such drug or device is in effect . . . ."

How long may the word "new" be used in promotional labeling and advertisements for a newly approved product, indication, or dosage form?

OPDP generally considers that "New" is an accurate description of the marketing phase for six months from the time a product is initially marketed. This should be distinguished from the time the product is cleared by FDA for marketing.

Does it matter where a package insert is placed on a labeling piece, such as on a calendar or a brochure with a pouch?

The package insert is required to accompany the labeling piece. OPDP also recommends that the labeling piece state clearly where the package insert is located.

Are package inserts required in all labeling pieces for products that are the same except for different strengths or dosages?

Yes. Even though products may be very similar, package inserts may be different for different dosage forms or different delivery systems for the same drug. The regulations would require a package insert for each dosage form and delivery system for which claims appear in the promotional labeling piece. Some drug products, however, have multi-dosage form package inserts. In those cases, the same package insert could be attached to each piece, even if the dosage forms or delivery systems were different.

Does a package insert in another language also have to be submitted in English?

Yes. Package inserts have to be submitted in English and not only in the foreign language.

Where do the regulations state the requirement for submitting prescription drug advertisements and labeling?

Under 21 C.F.R. 314.81(b)(3)(i):

Section 314.81 Postmarketing reports. 

    *****

(b) Reporting requirements.  The applicant shall submit to the Food and Drug Administration at the specified times two copies of the following reports:

    *****

(3) Other reporting--(i) Advertisements and promotional labeling. The applicant shall submit specimens of mailing pieces and any other labeling or advertising devised for promotion of the drug product . . . .

(See Selected Provisions of the Act and Regulations for the entire paragraph.)

When do promotional materials need to be submitted to OPDP?

Pursuant to 314.81(b)(3)(i), submissions must be made " . . . at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product."

Do all promotional materials for prescription drugs have to be submitted to OPDP?

The regulations for submitting materials apply to holders of NDAs, ANDAs, and antibiotic applications.  Manufacturers of pre-1938 products and products that have declared "not new drugs" are not required to submit specimens.  All products have labels and prescribing information, however, and products without approved labeling have permitted labeling.  Permitted labeling indicates FDA agrees with the label or labeling and permits its use. A manufacturer of a product with permitted labeling is responsible for assuring that advertisements and promotional labeling pieces are consistent with the product labeling.

What form should applicants use to submit materials to FDA?

Form FDA 2253 Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use.

How can I obtain a Form FDA 2253?

Form FDA 2253

To whom should I send the materials?

Food and Drug Administration
Center for Drug Evaluation and Research
Office of Prescription Drug Promotion
5901-B Ammendale Road
Beltsville, MD 20705-1266

Upon arrival, the material will be logged in for tracking and assigned to a reviewer in OPDP.

Who is responsible for submitting a Form FDA 2253 if the manufacturer and distributor are different companies?

Either company may submit the specimens, however, the applicant is ultimately responsible for compliance with 21 CFR 314.81(b)(3).

Can the layout or the way information is presented affect whether an advertisement or labeling piece is in compliance with the regulations?

Yes, 21 CFR 202.1(e)(7)(viii) states that an advertisement may be false, lacking in fair balance, or otherwise misleading if it:

"Fails to present information relating to side effects and contraindications with a prominence and readability reasonably comparable with the presentation of information relating to effectiveness of the drug, taking into account all implementing factors such as typography, layout, contrast, headlines, paragraphing, white space, and any other techniques apt to achieve emphasis."

For example, the presentation below of the word benefits and the word disadvantages would not be considered comparable. Although the words are the same point size, the color and contrast with the background make the word benefits much more noticeable than the word disadvantages.

Does FDA "approve" advertisements and promotional labeling before use by the company?

No, except in rare instances, when FDA may require pre-approval of promotional materials as part of an enforcement action.  However, DDMAC provides opinions on proposed advertisements and labeling pieces before use upon request by an applicant.  Note that accelerated approval products are under a "presubmission" requirement. The accelerated approval regulations require that applicants submit to FDA copies of all promotional materials prior to the intended date of dissemination or publication.

What is a reminder advertisement?

Under 202.1(e)(2)(i), reminder advertisements are identified as an exemption to the advertisement regulations, including the provisions under 202.1(e) to provide a brief summary.  Reminder advertisements " . . . call attention to the name of the drug product but do not include indications or dosage recommendations for use of the drug product. . . . and, optionally, information . . . containing no representation or suggestion relating to the advertised drug product."  Reminder advertisements cannot make a representation about the product or suggest a use for the product. 

What is reminder labeling?

Under 201.100(f), reminder labeling is " . . . labeling which calls attention to the name of the drug product but does not include indications or dosage recommendations for use. . . . and, optionally, information . . . containing no representation or suggestion relating to the drug product." Reminder labeling is exempted from the provisions under 201.100(d) to provide the full prescribing information.

Can a reminder advertisement compare one product to another or say one product is an alternative for another?

No. Such a comparison would imply the indication, and then the advertisement would no longer meet the exemption criteria.

Does FDA limit the amount of money that can be spent on reminder advertisements or reminder labeling pieces or regulate the types of objects (such as pens, cups, calendars, etc.) that can be used as reminder advertisements or reminder labeling pieces?

FDA regulations do not limit how much money companies may spend on reminder advertisements and labeling pieces, nor do the regulations limit the types of objects that can be used.  The regulations, however, limit the type of information that can be presented in reminder advertisements and labeling pieces, and not just the written information, but information that may be portrayed though graphics, design, or some other visual representation.

Series 2: Drug Drug Development requirements through the eyes of FDA

What are e-CTD? Understanding the various tools and softwares for Electronic submissions

The Electronic Common Technical Document (eCTD) is CDER/CBER’s standard format for electronic regulatory submissions. FDA as a government agency does not recommend specific software or tools. Information on tools, vendors, and eCTD preparation firms may be obtained by Internet search. Its recommend that you choose eCTD software and tools that allows you to build, validate, and view an eCTD.

In addition, there are several non-profit organizations that sponsor conferences and offer training in eCTD, and FDA regularly participates in these events. The FDA would like to work closely with people who plan to provide a submission using the eCTD specifications. Ther first step after would be to submit a sample eCTD for evaluation- Submission Process.

Quick Tips:-

• Reviewing the Published Guidance and Specifications documents
• Viewing  recent eCTD presentations by FDA staff
• Refer to the Comprehensive Table of Contents Headings and Hierarchy for information on document location, and for a regulatory and CFR mapping to the CTD
• Don’t rush when submitting, since what can seem like a small error can have big implications (such as a wrong digit in your application number
• Dont forget to take advantage of the Electronic Submissions Gateway and use FDA fillable forms and digital signatures for the fastest processing of your electronic submissions see the eCTD validation specifications for more information. Review the most recent eCTD presentations by FDA staff so you’re aware of current recommendations.
  If you have questions along the way, please do not hesitate to contact the CDER Electronic Submission (CDER ESUB) Support Team at esub@fda.hhs.gov

eCTD Guidance and Specifications

Electronic Submissions Public Docket 

Request a Pre-assigned Application Number for a Planned eCTD Submission

Guidance Documents

• Final Guidance for Industry: Providing Regulatory Submissions in Electronic Format--Human Pharmaceutical Applications and Related Submissions Using the eCTD Specifications (PDF - 132KB) (June 2008)
• Final Guidance for Industry: Integrated Summaries of Effectiveness and Safety: Location Within the Common Technical Document (PDF - 98KB) (April 2009)
  • Clarification for question #10 of "ICH M4: The CTD -- Efficacy Q&As" on submitting integrated summaries of safety and effectiveness (ISS/ISE) in the eCTD format (9/12/2006)

eCTD Specifications

• FDA eCTD Table of Contents Headings and Hierarchy (PDF - 73KB) (updated 7/6/2005)
• eCTD Backbone Files Specification for Module 1 (PDF - 102KB) (updated 12/13/2006)
  •  eCTD Module 1 Website - Updated Module 1 documents and supporting files - not for implementation(updated 8/6/2012)
• eCTD Backbone File Specification for Modules 2 through 5 3.2.2 (PDF - 726KB) (updated 7/16/2008)
• The eCTD Backbone File Specification for Study Tagging Files 2.6.1 (PDF - 149KB) (6/3/2008)
• Study Data Specifications (PDF - 199KB) (updated 7/18/2012)
• eCTD Validation Specifications Website (12/20/2011)
• Portable Document Format Specifications (PDF - 37KB) (updated 1/20/2012)
• Transmission Specifications (PDF - 35KB) (updated 7/26/2012)
  

UTILS	Version	File Name	MD5 Checksum	Support Began	Support Ends
ICH eCTD DTD	3.2	ich-ectd-3-2.dtd	1d6f631cc6b6357f0f4fe378e5f79a27	11/2003
ICH-STF DTD	2.2	ich-stf-v2-2.dtd	0972c10a4dadf3df5d2f41b2026a4a5c	8/2003
US Regional DTD	2.01	us-regional-v2-01.dtd	9d09aa5ffdb44368416e287f9b0ddeeb	8/2003
US Regional Stylesheet	1.1	us-regional.xsl	b3bdeb93158b2a30faca4d943b89fba4	9/2003
ICH eCTD Stylesheet	2.0	ectd-2-0.xsl	3a07a202455e954a2eb203c5bb443f77	11/2004
ICH STF Stylesheet	2-2a	ich-stf-stylesheet-2-2a.xsl	7af15705b92a21ac1a19527cfc504245	5/2007
Valid Values xml	2.2	valid-values.xml	664f584d0631db0414e8789e2a06613b	8/2008

 

Important Note: CDER's Office of Prescription Drug Promotion (formerly Division of Drug Marketing, Advertising and Communications - DDMAC) does not accept submissions in eCTD format or via the Electronic Secure Gateway at this time.  If received, these submissions will be rejected by CDER.

 

Submission Addresses for Electronic Documents

Send all electronic submissions (except ANDAs) to:
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room 
5901-B Ammendale Road
Beltsville, MD 20705-1266

Send ANDA submissions to:Office of Generic Drugs
Generic Drugs (HFD-600)
Center for Drug Evaluation and Research 
Food and Drug Administration
Metro Park North VII
7620 Standish Place
Rockville, MD 20855

General Considerations

• CDER and the Center for Biologics Evaluation and Research (CBER) have co-published a guidance document called Guidance for Industry: Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (PDF - 288KB). This document provides general information about the electronic submissions process.
• For more information on guidance documents, please contact esub@fda.hhs.gov.
   

Abbreviated New Drug Applications (ANDAs)

Please refer to:

• Abbreviated New Drug Application (ANDA): Generics
• ANDA Checklist (PDF - 122KB)

Drug Master Files (DMFs)

DMFs should be submitted in eCTD or paper format only. Please refer to:

• Guidance for Industry: Drug Master Files (DMFs)
• For general DMF questions, please contact dmfquestion@cder.fda.gov.
• For more information on electronic submissions for DMF, please contact esub@fda.hhs.gov.

 Investigational New Drug Applications (INDs)

CDER accepts INDs submitted in eCTD or paper format.  Please refer to:

• Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (PDF - 288KB)
• On March 26, 2002, FDA published the final guidance on the submission of INDs in electronic format to the Center for Biologics Evaluation and Research (CBER) (PDF - 80KB). Once the IND submission to CBER is posted on public docket 92S-0251, we will be capable of accepting INDs submitted to CBER in electronic format without paper copies. At this time, we are not extending this to INDs submitted to CDER.

 New Drug Applications (NDAs)

Please refer to:

• Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications (PDF - 288KB)

 FDA Electronic Submissions Gateway (ESG)

• FDA Electronic Submissions Gateway:CDER's preferred method of submission is via the FDA Electronic Submissions Gateway (ESG). For more information on the FDA ESG, see the Electronic Submissions Gateway page.
• Fillable Forms and Automated Processing:
  For automated processing of your submissions, submit an FDA fillable form with each submission. Using a fillable form with or without an additional signed scanned form (and no errors present in the submission) means the submission can be in the hands of the FDA Project Manager and Reviewers in as little as 10 minutes after it is successfully received by FDA via the ESG. This is applicable to both eCTD and non-eCTD submissions.
• Important Note:
  If, for some reason, you are unable to submit a fully completed fillable form, with an electronic signature, you could submit the completed fillable form (not scanned) without the signature and then provide a second 356h form that uses another method of signature (i.e., a scanned signature). When including a second complete 356h form, do not include "356h" anywhere in the file name. We recommend that you use a filename like "signed-form.pdf" or something similar, while the fillable form would be named "356h.pdf." This will allow our automated systems to correctly find your fillable form, read it, and process your submission appropriately.

 Electronic Document Room (EDR) / Physical Media

• Physical Media:
  When submitting via physical media, it is recommended that you submit a paper copy of the cover letter (with contact information) and FDA form in case the physical media proves to be unreadable. For more information, please refer to: Specification for Transmitting Electronic Submissions Using eCTD Specifications.
• All submissions on physical media should be sent to the EDR via the addresses at the top of this page. 
• Submissions on physical media are loaded and validated through the EDR.
• If you are submitting through the ESG, it is not necessary to also send physical media to the EDR.
• For more information on allowable file types or other questions dealing with electronic submissions,
• please contact: esub@fda.hhs.gov.

 

Declaration by the Blog owner:- All the information given above has been sourced out from the FDA website, for ease of young researchers to learn the method of drug registration process.