At a ground rounds lecture sponsored by a pharmaceutical company, the speaker’s slides look in part slick, cluttered and spiced with jargon as to outcomes. Later, in your office, a detail person focuses his spiel on an elaborate color triptych advertisement when speaking with you. You wonder why the ad you’re seeing now and the slides you had previously seen during the lecture both have a particular appearance and appear so similar.
Wonder no longer — the ad and the slides are all on file with the FDA and subject to the FDA’s rules.
The FDA has a plethora of rules and regulations that companies/detailers/physician speakers must comply with when presenting promotional materials for a drug. In this article, I’ll review some of these rules.
The Code of Federal Regulations
The Code of Federal Regulations that governs pharmaceutical companies (applicants for FDA approval of a medication) states the following:
(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 at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product.
Mailing pieces and labeling that are designed to contain samples of a drug product are required to be complete, except the sample of the drug product may be omitted.
Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product’s current professional labeling. Form FDA-2253 may be obtained from the PHS Forms and Publications Distribution Center, 12100 Parklawn Dr., Rockville, MD 20857. 21 CFR 314.81.
With an exception for special accelerated review for drugs seeking approval for serious or life-threatening diseases, rules mandate that pharmaceutical companies submit their promotional material to the FDA at the time of publication or distribution, not prior to use.
Hence, the majority of promotional materials for medications have not been pre-reviewed or pre-approved by the FDA — but will eventually receive such review and approval.
As a slide deck once finalized can sit on a shelf for weeks or months before its league of speakers hits the speaking circuit, it likely has been honed to FDA’s desires — which accounts for the particular look and feel of the PowerPoint presentation.
Physicians serving as paid speakers, or promoting medication as agents of a company (i.e. they are being paid) are supposed to adhere to the similar promotional guidelines and rules as sales and scientific staff of a pharmaceutical company because they’re representing a company or are acting on behalf of the company (per FDA guidelines).
Speakers are supposed to be trained by the pharmaceutical company on FDA regulations if they are being compensated by the pharmaceutical corporation (per Pharmaceutical Research and Manufacturers of America [PhRMA] guidelines: https://www.ama-assn.org/ama1/pub/upload/mm/437/ama_m2_ph.pdf. Speakers are considered agents for the companies that pay them.
Speakers’ Leeway
A speaker can use his or her own slides without FDA oversight if he or she created the slides, the talk is paid for by an independent accredited sponsoring company from an unrestricted grant on behalf of an ACCME accredited organization, and disclosures of conflicts of interest are made, and no product promotion by an industry representative takes place. In this kind of a talk, off-label, or even experimental, treatments can be discussed and CME credit awarded. This type of independent talk has become more common to get around the strictures of the FDA ways to use a medicine.
Within the FDA, the Division of Drug Marketing, Advertising and Communications (DDMAC) monitors all advertising and promotion of marketed prescription drug products. In addition, the DDMAC researches and writes guidance for industry. DDMAC reviewers work closely with other divisions in the FDA to assess the efficacy and other scientific claims touted in pharmaceutical promotional materials, and these reviewers interact closely with the FDA’s medical staff regarding the scientific basis of claims and products. (https://www.connectlive.com/events/drugdev/transcript-word.doc.)
The Code of Federal Regulations provides examples of labeling subjected to government regulation: Brochures, booklets, mailing pieces, detailing pieces, file cards, bulletins, price lists, catalogs, house organs, letters, motion picture films, film strips, lantern slides, sound recordings, exhibits, literature, and reprints and similar pieces of printed, audio or visual matter descriptive of a drug and references published (for example, the Physician’s Desk Reference) for use by medical practitioners, pharmacists or nurses, containing drug information supplied by the manufacturer, packer or distributor are hereby determined to be labeling as defined in section 201(m) of the Federal Food, Drug & Cosmetic Act.21 C.F.R. § 202.1(l)(2).
For more information about what is subject to government regulation, refer to the following:
Kordel v. United States, 335 U.S. 345 (1948). See 59 Fed. Reg. 59,820-01 (Nov. 18, 1994) (“The uses that are approved by the agency are sometimes referred to as ‘labeled’ uses because they appear in the approved labeling”).
David M. Fritch. Speak No Evil, Hear No Evil, Harm the Patient? Why the FDA Needs to Seek More, Rather Than Less, Speech from Drug Manufacturers on Off-Label Drug Treatments. Mich. St. J. Med. & Law. 315:9(2005).
A Rundown of the Process
After a medication received FDA approval, the pharmaceutical company making and selling the medication may promote the medication for the medication’s cleared or approved intended uses — i.e. its indication.
The pharmaceutical company may not introduce a drug by gaining approval to treat one disease, with the intention to treat another disease, which is an unapproved use.
The seller of a medication can not include data regarding unapproved uses for a medication in the medication’s labeling or promotional materials. If a pharmaceutical company promotes a medication off-label, the FDA can thereafter make a decision that the approved medication is “misbranded,” and illegal for sale, until the FDA evaluates and approves a new indication. (21 U.S.C. § 352.)
The FDA regulates pharmaceutical sales personnel according to its promotional activities. The FDA does not prescribe any particular training program for representatives, only that they obey FDA rules as they pertain to:
1. product labeling and package inserts
2. sales activities
3. advertising and marketing.
The information in the package insert must be based on data from adequate and well-controlled clinical trials that provide independent corroboration of a clinically relevant finding. This is the basis for a medication’s indication and labeling (package insert). The data do not have to be published in a peer-reviewed journal only, submitted in a fashion satisfactory to the FDA.
The Lowdown on Promotional Materials
Janet Lucy Rose, a consultant on FDA matters, gave an excellent presentation on the circumscription of promotional activity that I will utilize in the next several paragraphs (https://www.ama-assn.org/ama1/pub/upload/mm/437/ama_m2_ph.pdf).
The FDA regulations of companies clearly state that promotional materials must ensure the following:
• information about a prescription medication is not misleading
• any one acting on his or her behalf does not mislead by implication
• prior to FDA approval, promotion does not occur for unapproved products or unapproved uses of approved products
• information is consistent with the approved package insert and truthful and not misleading according to the package insert.
The Requirements for Detailing
The content of “detail” persons is also outlined by the FDA and they must:
• provide safety data about a medications (called “fair balance” i.e. safety and efficacy claims must be balanced) when discussing product attributes with a physician.
• leave a package insert with physicians when providing a sales call or printed information on a product.
Under the FDA , a “detail” person is allowed to do the following:
• as defined in the regulations, provide detailed information that is in the professional product labeling, or package insert, or is consistent with the package insert, or supported by substantial evidence.
• display and/or distribute company-approved promotional material and support material.
• refer “off-label” questions to the company’s medical relations/professional relations departments.
• sell using all company-approved material.
A detail person is not permitted to:
• prompt “off-label” queries regarding a medication.
• discuss product information that does not appear in a medications package insert.
• compare the package insert of a medication with the package insert of a competing medication as a general rule without data from a head-to-head trial as data can not be assumed to be equivalent.
If a physician needs to obtain information from a company, the department will:
• answer the questions with a narrowly tailored response.
• provide complete reprints (generally not just abstracts) of studies related to the question, even if it’s off-label.
• provide studies that accurately reflect all known information about that question, and not just the most favorable product profile.
FDA regulations do forbid promoting a medication to doctors based on:
• mechanism of action
• in vitro information supporting clinical claims or comparisons, unless scientific data exist effecting clinical outcomes.
What FDA Allows Speakers to Discuss
Based on FDA rules, speakers can make comparative claims between medications if there are:
• at least two adequate and well-controlled, head-to-head trials to buttress a comparative claim (and/or superiority and “equal efficacy or safety” claims) between two drugs.
• the same for medication promotion, whether the comparative data are or are not in the package insert.
• cannot make comparative claims unless the FDA has indicated both medications for the same indication.
Behind-the-Scenes Work
Much goes on behind the scenes before you ever see a slide presentation given on behalf of a company or view an advertising prop. Since you might be getting data that affect your practice, patients and prescribing habits, it is important for you to know.
At a ground rounds lecture sponsored by a pharmaceutical company, the speaker’s slides look in part slick, cluttered and spiced with jargon as to outcomes. Later, in your office, a detail person focuses his spiel on an elaborate color triptych advertisement when speaking with you. You wonder why the ad you’re seeing now and the slides you had previously seen during the lecture both have a particular appearance and appear so similar.
Wonder no longer — the ad and the slides are all on file with the FDA and subject to the FDA’s rules.
The FDA has a plethora of rules and regulations that companies/detailers/physician speakers must comply with when presenting promotional materials for a drug. In this article, I’ll review some of these rules.
The Code of Federal Regulations
The Code of Federal Regulations that governs pharmaceutical companies (applicants for FDA approval of a medication) states the following:
(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 at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product.
Mailing pieces and labeling that are designed to contain samples of a drug product are required to be complete, except the sample of the drug product may be omitted.
Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product’s current professional labeling. Form FDA-2253 may be obtained from the PHS Forms and Publications Distribution Center, 12100 Parklawn Dr., Rockville, MD 20857. 21 CFR 314.81.
With an exception for special accelerated review for drugs seeking approval for serious or life-threatening diseases, rules mandate that pharmaceutical companies submit their promotional material to the FDA at the time of publication or distribution, not prior to use.
Hence, the majority of promotional materials for medications have not been pre-reviewed or pre-approved by the FDA — but will eventually receive such review and approval.
As a slide deck once finalized can sit on a shelf for weeks or months before its league of speakers hits the speaking circuit, it likely has been honed to FDA’s desires — which accounts for the particular look and feel of the PowerPoint presentation.
Physicians serving as paid speakers, or promoting medication as agents of a company (i.e. they are being paid) are supposed to adhere to the similar promotional guidelines and rules as sales and scientific staff of a pharmaceutical company because they’re representing a company or are acting on behalf of the company (per FDA guidelines).
Speakers are supposed to be trained by the pharmaceutical company on FDA regulations if they are being compensated by the pharmaceutical corporation (per Pharmaceutical Research and Manufacturers of America [PhRMA] guidelines: https://www.ama-assn.org/ama1/pub/upload/mm/437/ama_m2_ph.pdf. Speakers are considered agents for the companies that pay them.
Speakers’ Leeway
A speaker can use his or her own slides without FDA oversight if he or she created the slides, the talk is paid for by an independent accredited sponsoring company from an unrestricted grant on behalf of an ACCME accredited organization, and disclosures of conflicts of interest are made, and no product promotion by an industry representative takes place. In this kind of a talk, off-label, or even experimental, treatments can be discussed and CME credit awarded. This type of independent talk has become more common to get around the strictures of the FDA ways to use a medicine.
Within the FDA, the Division of Drug Marketing, Advertising and Communications (DDMAC) monitors all advertising and promotion of marketed prescription drug products. In addition, the DDMAC researches and writes guidance for industry. DDMAC reviewers work closely with other divisions in the FDA to assess the efficacy and other scientific claims touted in pharmaceutical promotional materials, and these reviewers interact closely with the FDA’s medical staff regarding the scientific basis of claims and products. (https://www.connectlive.com/events/drugdev/transcript-word.doc.)
The Code of Federal Regulations provides examples of labeling subjected to government regulation: Brochures, booklets, mailing pieces, detailing pieces, file cards, bulletins, price lists, catalogs, house organs, letters, motion picture films, film strips, lantern slides, sound recordings, exhibits, literature, and reprints and similar pieces of printed, audio or visual matter descriptive of a drug and references published (for example, the Physician’s Desk Reference) for use by medical practitioners, pharmacists or nurses, containing drug information supplied by the manufacturer, packer or distributor are hereby determined to be labeling as defined in section 201(m) of the Federal Food, Drug & Cosmetic Act.21 C.F.R. § 202.1(l)(2).
For more information about what is subject to government regulation, refer to the following:
Kordel v. United States, 335 U.S. 345 (1948). See 59 Fed. Reg. 59,820-01 (Nov. 18, 1994) (“The uses that are approved by the agency are sometimes referred to as ‘labeled’ uses because they appear in the approved labeling”).
David M. Fritch. Speak No Evil, Hear No Evil, Harm the Patient? Why the FDA Needs to Seek More, Rather Than Less, Speech from Drug Manufacturers on Off-Label Drug Treatments. Mich. St. J. Med. & Law. 315:9(2005).
A Rundown of the Process
After a medication received FDA approval, the pharmaceutical company making and selling the medication may promote the medication for the medication’s cleared or approved intended uses — i.e. its indication.
The pharmaceutical company may not introduce a drug by gaining approval to treat one disease, with the intention to treat another disease, which is an unapproved use.
The seller of a medication can not include data regarding unapproved uses for a medication in the medication’s labeling or promotional materials. If a pharmaceutical company promotes a medication off-label, the FDA can thereafter make a decision that the approved medication is “misbranded,” and illegal for sale, until the FDA evaluates and approves a new indication. (21 U.S.C. § 352.)
The FDA regulates pharmaceutical sales personnel according to its promotional activities. The FDA does not prescribe any particular training program for representatives, only that they obey FDA rules as they pertain to:
1. product labeling and package inserts
2. sales activities
3. advertising and marketing.
The information in the package insert must be based on data from adequate and well-controlled clinical trials that provide independent corroboration of a clinically relevant finding. This is the basis for a medication’s indication and labeling (package insert). The data do not have to be published in a peer-reviewed journal only, submitted in a fashion satisfactory to the FDA.
The Lowdown on Promotional Materials
Janet Lucy Rose, a consultant on FDA matters, gave an excellent presentation on the circumscription of promotional activity that I will utilize in the next several paragraphs (https://www.ama-assn.org/ama1/pub/upload/mm/437/ama_m2_ph.pdf).
The FDA regulations of companies clearly state that promotional materials must ensure the following:
• information about a prescription medication is not misleading
• any one acting on his or her behalf does not mislead by implication
• prior to FDA approval, promotion does not occur for unapproved products or unapproved uses of approved products
• information is consistent with the approved package insert and truthful and not misleading according to the package insert.
The Requirements for Detailing
The content of “detail” persons is also outlined by the FDA and they must:
• provide safety data about a medications (called “fair balance” i.e. safety and efficacy claims must be balanced) when discussing product attributes with a physician.
• leave a package insert with physicians when providing a sales call or printed information on a product.
Under the FDA , a “detail” person is allowed to do the following:
• as defined in the regulations, provide detailed information that is in the professional product labeling, or package insert, or is consistent with the package insert, or supported by substantial evidence.
• display and/or distribute company-approved promotional material and support material.
• refer “off-label” questions to the company’s medical relations/professional relations departments.
• sell using all company-approved material.
A detail person is not permitted to:
• prompt “off-label” queries regarding a medication.
• discuss product information that does not appear in a medications package insert.
• compare the package insert of a medication with the package insert of a competing medication as a general rule without data from a head-to-head trial as data can not be assumed to be equivalent.
If a physician needs to obtain information from a company, the department will:
• answer the questions with a narrowly tailored response.
• provide complete reprints (generally not just abstracts) of studies related to the question, even if it’s off-label.
• provide studies that accurately reflect all known information about that question, and not just the most favorable product profile.
FDA regulations do forbid promoting a medication to doctors based on:
• mechanism of action
• in vitro information supporting clinical claims or comparisons, unless scientific data exist effecting clinical outcomes.
What FDA Allows Speakers to Discuss
Based on FDA rules, speakers can make comparative claims between medications if there are:
• at least two adequate and well-controlled, head-to-head trials to buttress a comparative claim (and/or superiority and “equal efficacy or safety” claims) between two drugs.
• the same for medication promotion, whether the comparative data are or are not in the package insert.
• cannot make comparative claims unless the FDA has indicated both medications for the same indication.
Behind-the-Scenes Work
Much goes on behind the scenes before you ever see a slide presentation given on behalf of a company or view an advertising prop. Since you might be getting data that affect your practice, patients and prescribing habits, it is important for you to know.
At a ground rounds lecture sponsored by a pharmaceutical company, the speaker’s slides look in part slick, cluttered and spiced with jargon as to outcomes. Later, in your office, a detail person focuses his spiel on an elaborate color triptych advertisement when speaking with you. You wonder why the ad you’re seeing now and the slides you had previously seen during the lecture both have a particular appearance and appear so similar.
Wonder no longer — the ad and the slides are all on file with the FDA and subject to the FDA’s rules.
The FDA has a plethora of rules and regulations that companies/detailers/physician speakers must comply with when presenting promotional materials for a drug. In this article, I’ll review some of these rules.
The Code of Federal Regulations
The Code of Federal Regulations that governs pharmaceutical companies (applicants for FDA approval of a medication) states the following:
(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 at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product.
Mailing pieces and labeling that are designed to contain samples of a drug product are required to be complete, except the sample of the drug product may be omitted.
Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product’s current professional labeling. Form FDA-2253 may be obtained from the PHS Forms and Publications Distribution Center, 12100 Parklawn Dr., Rockville, MD 20857. 21 CFR 314.81.
With an exception for special accelerated review for drugs seeking approval for serious or life-threatening diseases, rules mandate that pharmaceutical companies submit their promotional material to the FDA at the time of publication or distribution, not prior to use.
Hence, the majority of promotional materials for medications have not been pre-reviewed or pre-approved by the FDA — but will eventually receive such review and approval.
As a slide deck once finalized can sit on a shelf for weeks or months before its league of speakers hits the speaking circuit, it likely has been honed to FDA’s desires — which accounts for the particular look and feel of the PowerPoint presentation.
Physicians serving as paid speakers, or promoting medication as agents of a company (i.e. they are being paid) are supposed to adhere to the similar promotional guidelines and rules as sales and scientific staff of a pharmaceutical company because they’re representing a company or are acting on behalf of the company (per FDA guidelines).
Speakers are supposed to be trained by the pharmaceutical company on FDA regulations if they are being compensated by the pharmaceutical corporation (per Pharmaceutical Research and Manufacturers of America [PhRMA] guidelines: https://www.ama-assn.org/ama1/pub/upload/mm/437/ama_m2_ph.pdf. Speakers are considered agents for the companies that pay them.
Speakers’ Leeway
A speaker can use his or her own slides without FDA oversight if he or she created the slides, the talk is paid for by an independent accredited sponsoring company from an unrestricted grant on behalf of an ACCME accredited organization, and disclosures of conflicts of interest are made, and no product promotion by an industry representative takes place. In this kind of a talk, off-label, or even experimental, treatments can be discussed and CME credit awarded. This type of independent talk has become more common to get around the strictures of the FDA ways to use a medicine.
Within the FDA, the Division of Drug Marketing, Advertising and Communications (DDMAC) monitors all advertising and promotion of marketed prescription drug products. In addition, the DDMAC researches and writes guidance for industry. DDMAC reviewers work closely with other divisions in the FDA to assess the efficacy and other scientific claims touted in pharmaceutical promotional materials, and these reviewers interact closely with the FDA’s medical staff regarding the scientific basis of claims and products. (https://www.connectlive.com/events/drugdev/transcript-word.doc.)
The Code of Federal Regulations provides examples of labeling subjected to government regulation: Brochures, booklets, mailing pieces, detailing pieces, file cards, bulletins, price lists, catalogs, house organs, letters, motion picture films, film strips, lantern slides, sound recordings, exhibits, literature, and reprints and similar pieces of printed, audio or visual matter descriptive of a drug and references published (for example, the Physician’s Desk Reference) for use by medical practitioners, pharmacists or nurses, containing drug information supplied by the manufacturer, packer or distributor are hereby determined to be labeling as defined in section 201(m) of the Federal Food, Drug & Cosmetic Act.21 C.F.R. § 202.1(l)(2).
For more information about what is subject to government regulation, refer to the following:
Kordel v. United States, 335 U.S. 345 (1948). See 59 Fed. Reg. 59,820-01 (Nov. 18, 1994) (“The uses that are approved by the agency are sometimes referred to as ‘labeled’ uses because they appear in the approved labeling”).
David M. Fritch. Speak No Evil, Hear No Evil, Harm the Patient? Why the FDA Needs to Seek More, Rather Than Less, Speech from Drug Manufacturers on Off-Label Drug Treatments. Mich. St. J. Med. & Law. 315:9(2005).
A Rundown of the Process
After a medication received FDA approval, the pharmaceutical company making and selling the medication may promote the medication for the medication’s cleared or approved intended uses — i.e. its indication.
The pharmaceutical company may not introduce a drug by gaining approval to treat one disease, with the intention to treat another disease, which is an unapproved use.
The seller of a medication can not include data regarding unapproved uses for a medication in the medication’s labeling or promotional materials. If a pharmaceutical company promotes a medication off-label, the FDA can thereafter make a decision that the approved medication is “misbranded,” and illegal for sale, until the FDA evaluates and approves a new indication. (21 U.S.C. § 352.)
The FDA regulates pharmaceutical sales personnel according to its promotional activities. The FDA does not prescribe any particular training program for representatives, only that they obey FDA rules as they pertain to:
1. product labeling and package inserts
2. sales activities
3. advertising and marketing.
The information in the package insert must be based on data from adequate and well-controlled clinical trials that provide independent corroboration of a clinically relevant finding. This is the basis for a medication’s indication and labeling (package insert). The data do not have to be published in a peer-reviewed journal only, submitted in a fashion satisfactory to the FDA.
The Lowdown on Promotional Materials
Janet Lucy Rose, a consultant on FDA matters, gave an excellent presentation on the circumscription of promotional activity that I will utilize in the next several paragraphs (https://www.ama-assn.org/ama1/pub/upload/mm/437/ama_m2_ph.pdf).
The FDA regulations of companies clearly state that promotional materials must ensure the following:
• information about a prescription medication is not misleading
• any one acting on his or her behalf does not mislead by implication
• prior to FDA approval, promotion does not occur for unapproved products or unapproved uses of approved products
• information is consistent with the approved package insert and truthful and not misleading according to the package insert.
The Requirements for Detailing
The content of “detail” persons is also outlined by the FDA and they must:
• provide safety data about a medications (called “fair balance” i.e. safety and efficacy claims must be balanced) when discussing product attributes with a physician.
• leave a package insert with physicians when providing a sales call or printed information on a product.
Under the FDA , a “detail” person is allowed to do the following:
• as defined in the regulations, provide detailed information that is in the professional product labeling, or package insert, or is consistent with the package insert, or supported by substantial evidence.
• display and/or distribute company-approved promotional material and support material.
• refer “off-label” questions to the company’s medical relations/professional relations departments.
• sell using all company-approved material.
A detail person is not permitted to:
• prompt “off-label” queries regarding a medication.
• discuss product information that does not appear in a medications package insert.
• compare the package insert of a medication with the package insert of a competing medication as a general rule without data from a head-to-head trial as data can not be assumed to be equivalent.
If a physician needs to obtain information from a company, the department will:
• answer the questions with a narrowly tailored response.
• provide complete reprints (generally not just abstracts) of studies related to the question, even if it’s off-label.
• provide studies that accurately reflect all known information about that question, and not just the most favorable product profile.
FDA regulations do forbid promoting a medication to doctors based on:
• mechanism of action
• in vitro information supporting clinical claims or comparisons, unless scientific data exist effecting clinical outcomes.
What FDA Allows Speakers to Discuss
Based on FDA rules, speakers can make comparative claims between medications if there are:
• at least two adequate and well-controlled, head-to-head trials to buttress a comparative claim (and/or superiority and “equal efficacy or safety” claims) between two drugs.
• the same for medication promotion, whether the comparative data are or are not in the package insert.
• cannot make comparative claims unless the FDA has indicated both medications for the same indication.
Behind-the-Scenes Work
Much goes on behind the scenes before you ever see a slide presentation given on behalf of a company or view an advertising prop. Since you might be getting data that affect your practice, patients and prescribing habits, it is important for you to know.
