As reported by our sister site, Health Industry Washington Watch, on Wednesday the House Energy and Commerce Health Subcommittee will hold a hearing entitled, "Drug Safety: An Update from the FDA." At the hearing, the FDA will detail its current challenges and successes in the area of drug safety. Joshua M. Sharfstein, M.D., FDA Principal Deputy Commissioner, is slated to testify.
Ralph Tyler has been appointed the new FDA General Counsel. The announcement was made today by FDA Commissioner, Dr. Margaret A. Hamburg. Mr. Tyler will join the Office of the Chief Counsel in Rockville, MD on January 19, 2010. Stepping down will be Acting Chief Counsel Michael Landa, who will return to the Center for Food Safety and Nutrition (CFSAN) as Deputy Director for Regulatory Affairs.
Mr. Tyler is currently the Insurance Commissioner of the State of Maryland. Previously he served as Chief Legal Counsel to Maryland Governor Martin O’Malley. Prior to that, Mr. Tyler served as the Deputy Attorney General, the Chief of Litigation, and Assistant Attorney General in the Maryland Attorney General’s office between 1982 and 1996. Mr. Tyler also spent several years as a partner at Hogan & Hartson, LLP. He holds a B.A. from the University of Illinois, a J.D. from Case Western Reserve University, and a LL.M. from Harvard University.
This post was written by Areta Kupchyk, Kevin Madagan, and Paul Sheives.
Following a decade-long hiatus, the Food and Drug Administration (“FDA”) appears ready to finally address industry Internet communications. FDA’s Center for Drug Evaluation and Research (“CDER”) in collaboration with other divisions within FDA, held a two-day hearing on November 12th and 13th to help the Agency determine how the statutory provisions, regulations, and policies governing advertising and promotional labeling should be applied to product-related information on the Internet and emerging technologies.
Much has changed since 1996, the last time FDA held a public hearing on this topic. The Internet is now widely used as a medium for companies to disseminate information about their products, and the Internet's ability to facilitate communication and collaboration has substantially evolved over the last few years primarily as a result of a second (Web 2.0) and now third (Web 3.0) generation of Internet development and website design. The inherent flexibility and intelligence of Web 2.0 and 3.0 is great for society, but also fraught with risk for an FDA-regulated industry that must carefully control its interactions with consumers and health care practitioners. Indeed, the industry has largely avoided using Web 2.0 out of fear that any social media use may result in FDA enforcement action.
Given the above, it is not surprising that FDA’s hearing was a welcome relief to many. Even though the hearing technically was only an information gathering exercise for FDA, it was an important opportunity for industry leaders and stakeholders to contribute to FDA’s emerging Internet policy. This Client Alert provides a brief summary of the major themes and recommendations from the presenters at the hearing.
In addition, please see a related commentary on the blog Adlaw by Request (“FDA Seeks To Understand Social Media”). Adlaw by Request is a blog designed to provide regular news on advertising law developments in the United States and elsewhere, with practical commentary and analysis from Reed Smith’s Advertising, Technology and Media (ATM) practice.
This post was written by Dana Blanton.
On November 12 and 13, 2009, the FDA hosted public hearings to vet the potential need for regulation of prescription pharmaceutical and medical device marketing on social media outlets such as YouTube, Wikipedia, Facebook, and Twitter. The FDA specifically sought input on these five questions: (1) For what online communications are manufacturers, packers or distributors accountable? (2) How can manufacturers, packers, or distributors fulfill regulatory requirements in their Internet and social media promotion, particularly when using tools that are associated with space limitations and tools that allow for real-time communications? (3) What parameters should apply to the posting of corrective information on Web sites controlled by third parties? (4) When is the use of links appropriate? and (5) Questions specific to Internet adverse event reporting.
The hearings attracted both internet and ethical drug and device industry giants, as well as nonprofit organizations seeking to gain a better understanding of what will certainly be a new frontier for advertising these regulated products. The FDA's existing regulations for print and television advertising are widely considered unsuitable for social media outlets, some of which allow for no more than 140 characters per post--far too few to include FDA-mandated safety information--and most of which allow for uncensored layperson commentary sometimes indistinguishable from manufacturer content. As a result, pharma and medical device representatives reported, drug and device companies have been reluctant to venture into the social media advertising field. Meanwhile, media and marketing firms offered pre-packaged advertising solutions and industry critics suggested that the FDA and pharmaceutical and device companies should bear the burden of correcting misinformation on third party websites and blogs. The FDA will consider the commentary and determine whether guidelines should be promulgated.
Information on the hearing, including background, further information regarding the five issues presented, a link to transcripts of the FDA's 1996 hearing on internet advertising and other information may be found in the Federal Register Notice for the hearing and transcripts of the November 12 and 13, 2009 hearings will be available by approximately December 13, 2009.
This post was written by Frederick H. Branding, R.Ph., JD, Areta L. Kupchyk and Kevin M. Madagan.
“The FDA must be vigilant, the FDA must be strategic, the FDA must be quick, and the FDA must be visible,” according to Commissioner Hamburg. She stated that vigilance means regular inspections and follow-up to ensure problems are resolved; identifying and resolving problems early; a “greater emphasis on significant risk and violations”; rapidly responding to egregious violations or violations that jeopardize public health; and using “meaningful penalties to send a strong message” to discourage future offenses. The Commissioner also said that the agency must be visible and publicize its enforcement actions (and the rationale for those actions) widely and effectively. Commissioner Hamburg described six new policy changes to meet these goals.
1. 15 Day Post-Inspection Deadline
FDA will now set post-inspection deadlines. When FDA finds that a firm is significantly out of compliance and issues inspectional observations on Form FDA-483, it will expect a prompt response, generally no more than 15 days. Failing to respond in 15 days will trigger FDA to move forward with a warning letter or enforcement action.
2. Streamlined Warning Letter Process – Chief Counsel Pre-Review Policy Abandoned
Abandoning a policy implemented in 2002, FDA’s Chief Counsel Office will no longer review every warning letter issued by the agency. The Chief Counsel will limit warning letter review to significant legal issues only. In other words regional offices will now be permitted to issue warning letters.
3. Closer Collaboration with Regional Partners
FDA will continue to seek to work more closely with regulatory partners (e.g., state, local, and international officials) to develop risk control and enforcement strategies, as these entities have more authority to take action quickly than FDA. “When the public health is at risk, the FDA will reach out to our partners to take rapid action while we alert the public and prepare longer-term responses.”
4. Prioritize Enforcement Follow-Up
FDA will prioritize its follow-up with non-compliant firms. After a warning letter is issued or a product recall occurs, FDA will “make it a priority to follow up promptly with appropriate action.” This may include an inspection or investigation to ensure the problem has been resolved.
5. Swift and Aggressive Action Without a Warning Letter
FDA is prepared to take swift aggressive action to protect the public. The agency will no longer issue multiple warning letters. In addition, FDA will consider immediate action, such as action before it issues a warning letter, to address significant health concerns or egregious violations. Although FDA has had the authority to take enforcement action without issuing a warning letter, the agency generally reserves use of enforcement actions such as seizure or injunction for serious public safety situations requiring immediate action to stop manufacturing or distribution to prevent harm.
6. Warning Letter “Close-Out” Process
FDA is developing a formal warning letter close-out process. For example, after FDA reinspects a facility to ensure that a firm has fully corrected violations identified in a warning letter, FDA may provide to the firm a formal “close-out” letter, indicating that the issues have been successfully addressed. This letter will then be posted on FDA’s website. However, not every warning letter will be eligible for a formal close-out letter. Such letters will likely be sent to companies with a history of ongoing violations.
Commissioner Hamburg expects these new policies will ensure violative inspection results are taken seriously, warning letters and enforcement actions occur in a timely manner, and steps are taken promptly to protect consumers.
On August 4, 2009 at 2:30 p.m., it will be the Senate's HELP Committee's turn to hold a hearing entitled "Protecting Patients from Defective Medical Devices". No witness list is yet posted.
For our coverage on past hearings on this issue, click here.
This post was written by Frederick H. Branding, R.Ph., JD and Kevin M. Madagan.
Numerous signals by the Food and Drug Administration (“FDA”) in recent weeks, including statements made by Dr. Margaret A. Hamburg, the recently appointed FDA Commissioner, show that the agency intends to toughen enforcement in several areas. These signals should be taken seriously. An “awakened” FDA will be funded with additional monies promised for FDA’s budget and with funding proposed through legislation such as The Drug and Device Accountability Act of 2009 (S. 882). As a result, firms that manufacture, import, and distribute FDA-regulated products can anticipate being visited more often, and probably more critically, than in the past. This, in turn, will force a company to handle additional Inspectional Observations (FDA 483s), Warning Letters, and reinforcement actions.
This article discusses two areas in which FDA has begun to focus – supply chains and imports, in particular supply chain management and safety, and increased foreign and domestic import inspections. Included in the discussion are suggestions companies may wish to consider in preparing for increased regulatory scrutiny.
To read the full alert, click here.
The article on "Prescription Drug and Medical Device Promotion – New FDA Draft Guidance on Presenting Risk Information" by Reed Smith lawyers Areta Kupchyk, Frederick Branding, Jennifer Goldstein and Kevin Madagan (previously discussed in this post) has now been published in AHLA's Health Lawyers Weekly (log in required).
The Reed Smith Health Industry Washington Watch blog has been updated to discuss a variety of health policy developments, including the following:
This post was written by Areta Kupchyk, Frederick Branding, Jennifer Goldstein and Kevin Madagan.
On May 27, 2009, the Food and Drug Administration (“FDA”) announced the availability of a draft guidance titled “Presenting Risk Information in Prescription Drug and Medical Device Promotion” (“Draft Guidance”). The Draft Guidance sets forth the standards FDA intends to consider when evaluating promotional pieces to determine whether they effectively communicate risk information in a non-misleading manner. Under the Food, Drug & Cosmetic Act (“FDCA”) and FDA’s implementing regulations, promotional materials making claims about a product are deemed misleading if they fail to disclose certain information about the product’s risks. FDA is accepting comments on the draft through Aug. 25, 2009. Reed Smith’s full alert provides a brief outline of the Draft Guidance and identifies issues for possible comment to FDA.
The FDA has issued final guidance regarding formal meetings between FDA and sponsors or applicants relating to the development and review of drug or biological drug products by the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research (note that the guidance does not apply to abbreviated new drug applications). Specifically, the guidance discusses the principles of good meeting management practices and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting formal meetings. The document supersedes the guidance entitled “Formal Meetings With Sponsors and Applicants for PDUFA Products” published in February 2000.
On May 27, 2009, the Food and Drug Administration (FDA) published a notice soliciting comments on a draft guidance document entitled “Presenting Risk Information in Prescription Drug and Medical Device Promotion.” The draft guidance proposes to use a “reasonable consumer” standard, similar to the Federal Trade Commission's standard, for assessing whether advertisements are misleading, a standard FDA already applies to labels on food and dietary supplements. In the draft guidance, FDA discusses the factors the agency would consider when evaluating prescription drug and restricted device promotional materials directed at healthcare professionals and consumers. The factors include: consistent and appropriate use of language, use of signals, framing of risk information, and the hierarchy of risk information. FDA also states that the agency will review content for both quantity of risk information, as well as materiality and comprehensiveness. Finally, FDA provides extensive factors it considers when evaluating the format of promotional materials. Comments should be submitted by August 25, 2009; for information on submitting comments, click here.
Washington Legal Foundation's latest Legal Backgrounder, the "Logic of Michigan's 'FDA Defense' Survives Recent Supreme Court Ruling", authored by Thomas J. Foley, explains why the Wyeth v. Levine, 129 S.Ct. 1187 (2009) ruling does not support a rationale to overturn Michigan law that provides a defense against drug product liability suits where the manufacturer obtained FDA approval.
On May 12, 2009 the Subcommittee on Health, of the Committee on Energy and Commerce, House of Representatives, held a hearing on H.R. 1346, the "Medical Device Safety Act of 2009". If passed, it would overturn the Supreme Court decision, Riegel v. Medtronic, Inc., 128 S.Ct. 999 (2008), which held that under the express preemption clause of the Medical Devices Amendment of 1976 (MDA), the federal requirements created by the premarket approval process for Class III devices preempted state law tort claims that added or differed from the federal requirements. This hearing comes at the heels of public and media scrutiny of this decision, including last year's House Committee on Oversight and Government Reform preemption hearing held May 14, 2008 and the Senate Judiciary Committee's preemption hearing held June 11, 2008.
Before the invited panel of witnesses spoke, numerous members of the subcommittee provided opening remarks, which reflected the division among those who argued that the Supreme Court's analysis in Riegel departed from the legislative intent of the MDA, and those who agreed that the pending legislation would prevent innovation and access to medical devices that are life-saving. Arguments against the bill also noted that moving against preemption would otherwise place safety concerns in the hands of juries across the country, instead of on the FDA's safety and efficacy evaluations. Some focus was also placed on the FDA's effectiveness in policing the manufacturers, with several congress members such as Representative John Dingell, MI and Henry Waxman, CA arguing that the FDA has not been able to identify and take action on defective products, therefore calling into question their effectiveness in ensuring safety, while other congress members such as Representatives Steve Buyer, IN and Michael Burgess, TX argued that if the FDA is underfunded and without resources, the Committee should focus on the FDA, not on tort reform.
Most of the invited witnesses were repeat appearances from last year's hearing. David Vladeck, J.D., Professor of Law, Georgetown University Law Center presented his case in support of the bill, and repeated his concerns about the Riegel court's alleged deviation from congressional intent as reflected in legislative history. He also argued that manufacturers brought the express preemption defense to fore and that it was a more recent phenomena since the mid 1990s, after the Cipollone v. Liggett Group, Inc., 505 U.S. 504, 517, 112 S.Ct. 2608, 2618 (1992) decision.
William H. Maisel, M.D., M.P.H., Director, Medical Device Safety Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Boston also testified, as both a practicing cardiologist and as a consultant and advisory committee member for the FDA. He provided anecdotal background with what he represented as an example of a man who was implanted with a St. Jude pacemaker that allegedly was subjected to a recall and resulted in additional surgical procedures. In making this example, Dr. Maisel argued that the self-interest of companies are at odds with the congressional goal of ensuring public safety. Gregory Curfman, M.D., Executive Editor, New England Journal of Medicine also echoed similar sentiments, and discounted the arguments made about innovation and safety for consumers being mutually exclusive.
Richard Cooper of the law firm Williams & Connolly LLP provided a big-picture review of what it would mean to have 50 state juries take the place of the FDA and seasoned clinicians when determining what constitutes a "defect" meriting liability. Mr. Cooper also emphasized that innovation would be hampered should preemption be denied to medical device companies, noting how many smaller companies that are focused on under-served areas of practice would be litigated out of their market share.
Bridget Robb of Pennsylvania and Michael Kinsley of Washington both presented anecdotal history with medical devices. Ms. Robb testified about her experience with a cardiac lead that she claimed unnecessarily shocked her and caused grievous subsequent emotional and physical injury, while Mr. Kinsley presented his story of how deep brain stimulation and other implanted medical devices has allowed him to lead a productive life despite a Parkinson's Disease diagnosis. Both presented different takes on the limits of how much risk a patient should face when balanced with the potential benefits offered by their medical devices.
Prior to the hearing, the Energy & Commerce Committee also published a letter asking the FDA to reexamine its decision to approve a medical device called the "collagen scaffold" that is used to reinforce and repair the meniscus, which is a natural cushion in the knee. This letter, as addressed to the FDA Principal Deputy Commissioner, seeks reexamination of the approval decision that the authors argue was made over the objection of FDA scientists.
For more information, please see the previous post "Will The May 12 Hearing On The "Medical Device Safety Act of 2009" Recognize The Costs Of Eliminating Preemption?"
This post was written by Areta L. Kupchyk, James M. Wood and Kevin M. Madagan.
FDA's Good Reprint Practice (GRP) Guidance went into effect in January 2009. The GRP Guidance establishes criteria that FDA will now use to determine whether the distribution of medical or scientific reprints and reference texts about off-label uses of a drug or device would constitute impermissible promotional activity under the Food, Drug and Cosmetic Act.
Read Reed Smith’s full commentary analyzing the GRP Guidance, which includes a Good Reprint Practice Checklist.
The FDA published a notice on January 13, 2009 announcing a final guidance document entitled “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices.” The guidance, which finalizes a February 20, 2008 draft policy, is intended to provide manufacturers with the agency's views on permissible distribution by a company's sales representatives of medical journal articles and scientific or medical reference publications that discuss unapproved new uses for FDA-approved drugs or biologics or FDA-approved or cleared medical devices to healthcare professionals. As with the 2008 draft guidance, the final version notes the need to balance the law’s prohibition on distributing or promoting “unapproved uses of approved drugs and approved or cleared medical devices” with the “important public policy” of providing information that “may even constitute a medically recognized standard of care.” The FDA concludes that the touchstone for lawful dissemination of literature about unapproved uses is that the publications “are truthful and non-misleading.” To meet this standard, the FDA final guidance lists “principles of Good Reprint Practices” that include criteria for determining the type of publication and the manner in which the publication can be distributed. Although the final guidance closely tracks the draft guidance, it has some important clarifications, including revisions to the Good Reprint Practices and a specific reference encouraging manufacturers to seek approvals and clearance for new indications and intended uses for medical products. A Reed Smith analysis of the final guidance is available here.
The FDA published a notice January 15, 2009 announcing the launch of a voluntary Secure Supply Chain pilot program to help promote the safety of imported drugs and active pharmaceutical ingredients (APIs). According to the FDA, the program would enable the FDA to focus its resources on imported drugs that fall outside the program and that pose a risk of being adulterated, misbranded, or unapproved, while increasing the likelihood of expedited entry for specific finished drug products and APIs into the U.S. that meet the pilot’s criteria. The FDA plans to select 100 applicants to participate in the program, and each applicant may designate up to five drugs for selection in the pilot program. To qualify, applicants will need to meet the pilot's criteria, including a requirement that they maintain control over the drugs from the time of manufacture through entry into the U.S. The FDA will accept comments on the program through March 16, 2009.
On January 13, 2009, the FDA published a notice seeking comments on issues related to the enrollment of certain populations in clinical drug trials. This request is related to FDA's implementation of the Food and Drug Administration Amendments Act of 2007 (FDAAA) section 901, which requires the FDA to report to Congress on best practice approaches to increasing participation of elderly populations, children, racially and ethnically diverse communities, and medically-underserved populations in clinical drug trials. FDA requests comments from medical product manufacturers, IRBs, patient groups, researchers, and other interested parties on possible approaches to increasing participation of these groups in clinical drug trials. Comments will be accepted until February 27, 2009.
On January 13, 2009, the FDA announced on behalf of the Interagency Working Group on Import Safety the availability of draft guidance on “Good Importer Practices.” The draft guidance document provides general recommendations to importers on possible practices and procedures they may follow to increase the likelihood the products they import (including drugs) comply with applicable U.S. safety and security requirements. Comments will be accepted through April 13, 2009.
On January 16, 2009, the FDA published a final rule requiring an abbreviated new drug application (ANDA) applicant to submit data from all bioequivalence (BE) studies the applicant conducts on a drug product formulation submitted for approval. In the past, ANDA applicants have submitted BE studies demonstrating that a generic product meets bioequivalence criteria in order for FDA to approve the ANDA, but have not typically submitted additional BE studies conducted on the same drug product formulation, such as studies that do not show that the product meets these criteria. The FDA now believes that additional BE study data may be important in determining whether the proposed formulation is bioequivalent to the reference listed drug, and will increase FDA’s understanding of how changes in components, composition, and methods of manufacture may affect product formulation performance. The rule is effective July 15, 2009.
The FDA has released a draft document entitled “Guidance for Industry: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps).” The draft document provides establishments that manufacture HCT/Ps with recommendations for complying with CGTP requirements. This guidance also addresses whether the establishment registration and HCT/P listing requirements under 21 CFR part 1271, subparts A and B apply in certain instances. The FDA will accept comments on the guidance through April 16, 2009.
The FDA has released draft guidance on “Standards for Securing the Drug Supply Chain – Standardized Numerical Identification for Prescription Drug Packages,” which recommends standards industry should use for the identification of individual packages containing prescription drugs under the FDAAA. The standards are designed to facilitate adoption of a uniform electronic track and trace system for prescription drugs to further improve their safety and security. The FDA is soliciting comments on certain aspects of the guidance, as detailed in a January 16, 2009 notice. Comments will be accepted until April 16, 2009.
The FDA has released final guidance on “Certifications To Accompany Drug, Biological Product, and Device Applications/Submissions: Compliance with Section 402(j) of The Public Health Service Act, Added By Title VIII of The Food and Drug Administration Amendments Act of 2007.” The guidance describes the FDA’s current thinking regarding the types of applications and submissions that sponsors, industry, researchers, and investigators submit to FDA and accompanying certifications under the FDAAA related to the submission of required information to the clinical trials data bank, www.ClinicalTrials.gov.
On January 16, 2009, the FDA published a notice announcing “Draft Guidance for Industry on Submission of Laboratory Packages by Accredited Laboratories,” which is intended to enhance the quality and reliability of test results submitted by importers to demonstrate that their products meet the FDA's requirements. The guidance advises importers how to use accredited laboratories and makes recommendations about the quality and type of test data that these laboratories should produce to support test results submitted to the FDA. According to an FDA press release, the guidance also is intended to reduce the likelihood that an importer will submit only favorable test results to the FDA. Comments on the draft will be accepted through April 16, 2009.
The GAO has issued a report entitled "Medical Devices: FDA Should Take Steps to Ensure That High-Risk Device Types Are Approved through the Most Stringent Premarket Review Process." The report was issued in response to a provision of the FDA Amendments Act of 2007 mandating that GAO study the 510(k) process. The GAO found that in fiscal years 2003 through 2007, as part of its premarket review to determine whether devices should be permitted to be marketed in the United States, FDA:
Although Congress envisioned that class III devices would be approved through the more stringent PMA process, and the Safe Medical Devices Act of 1990 required that FDA either reclassify or establish a schedule for requiring PMAs for class III device types, the GAO concluded that this process remains incomplete. GAO found that in fiscal years 2003 through 2007 FDA cleared submissions for 24 types of class III devices through the 510(k) process. As of October 2008, four of these device types had been reclassified to class II, but 20 device types could still be cleared through the 510(k) process. FDA officials said that the agency is committed to issuing regulations either reclassifying or requiring PMAs for the class III devices currently allowed to receive clearance for marketing via the 510(k) process, but did not provide a time frame for doing so.
GAO recommends that FDA expeditiously take steps to issue regulations for class III device types currently allowed to enter the market via the 510(k) process by requiring PMAs or reclassifying them to a lower class. HHS agreed with GAO’s recommendation.
Click here to view the report.
This post was written by Areta L. Kupchyk, James M. Wood and Kevin Madagan.
On January 13, 2009, eleven months after the Food and Drug Administration (FDA) issued a draft guidance document, and 2 1/2 years after the sunset of the statute intended to permit the dissemination of medical literature about unapproved uses of drugs and medical devices, the FDA issued a final guideline for such dissemination. Often referred to as “the distribution of off-label use journal articles,” FDA’s final guidance is aptly named “Guidance For Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices.”
As with the 2008 draft guidance, the final version begins by succinctly discussing the historical attempts to regulate the distribution of literature about unapproved uses, including noting the need to balance the law’s prohibition on distributing or promoting “unapproved uses of approved drugs and approved or cleared medical devices” with the “important public policy” of providing information that “may even constitute a medically recognized standard of care.” FDA concludes that the touchstone for lawful dissemination of literature about unapproved uses is that the publications “are truthful and non-misleading.”
To meet this standard, the FDA final guidance lists “principles of Good Reprint Practices” that include criteria for determining the type of publication, and the manner in which the publication can be distributed. Although the final guidance closely tracks the draft guidance, it has some important clarifications.
Click here to read the full alert, which highlights these clarifications and provides an overview of the final guidance.
UPDATE: Much obliged to Drug and Device Law for the link and thoughtful discussion, and more also is at the FDA Law Blog.
The Food and Drug Administration Amendments Act of 2007 (FDAAA) expanded the public reporting requirements for “applicable clinical trials” involving certain drugs, biologicals, and devices. In December 2008, the Food and Drug Administration (FDA) issued a draft guidance document proposing, among other things, definitions that would affect who would be required to register certain clinical trials under the FDAAA. In some cases, FDA's proposal would require manufacturers who make grants to investigators to be the responsible party required to register. In addition, FDA elaborates on the circumstances under which clinical investigations designed to demonstrate bioequivalency would be subject to reporting. Additional background information is available at the clinicaltrials.gov web site. Reed Smith is reviewing the draft guidance. Please contact Areta Kupchyk at akupchyk@reedsmith.com for more information.
The FDA has released final guidance on “Substantiation for Dietary Supplement Claims Made Under Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act,” which discusses the amount, type, and quality of evidence that FDA recommends a dietary supplement manufacturer have to substantiate a nutritional deficiency, structure/function, or general well-being claim. FDA has adopted the FTC standard for substantiation and, among other things, will expect statistically significant clinical studies to support structure/function claims. For more information, contact Areta Kupchyk at akupchyk@reedsmith.com.
The FDA has issued final guidance on “Labeling OTC Human Drug Products—Questions and Answers.” This document is intended to assist manufacturers, packers, and distributors of over-the-counter (OTC) drug products in complying with the agency’s regulation on standardized content and format requirements for the labeling of OTC drug products, including the use of toll-free numbers and compliance with adverse event reporting requirements.
The FDA has released draft guidance entitled “Assay Migration Studies for In Vitro Diagnostic Devices,” which is designed to present a least burdensome regulatory approach to gaining FDA approval of Class III or certain licensed in vitro diagnostic devices in cases when a previously-approved assay is migrating to a new system for which the assay has not been previously approved or licensed. FDA will accept comments on the draft guidance until April 6, 2009.
The FDA is inviting pharmaceutical companies to participate in the FDA’s Regulatory Project Management Site Tours and Regulatory Interaction Program, through which FDA personnel observe operations of pharmaceutical manufacturing and/or packaging facilities, pathology/toxicology laboratories, and regulatory affairs operations. The goals of the program are to provide FDA regulatory project managers with first-hand exposure to industry’s drug development processes, and to offer a venue for sharing information about project management procedures (but not drug-specific information) with industry representatives. Interested companies may submit proposed agendas to FDA by March 6, 2009.
FDA is soliciting comments on the paperwork burden associated with its plan to require drug establishment registration and drug listing submissions in electronic format. Comments will be accepted until February 9, 2009.
On October 28, 2008, the Food and Drug Administration (FDA) published a final rule requiring a statement to be included on certain human drug product labeling that provides a toll-free number for reporting side effects and specifies that the number is not intended to be used for medical advice. The rule, which confirms a January 3, 2008 interim final rule on this issue, implements provisions of the Best Pharmaceuticals for Children Act and the Food and Drug Administration Amendments Act of 2007. The compliance date for the final rule is July 1, 2009 (rather than the January 1, 2009 compliance date anticipated under the interim final rule).
On October 22, 2008, the Government Accountability Office (GAO) issued a report entitled "Drug Safety: Better Data Management and More Inspections Are Needed to Strengthen FDA's Foreign Drug Inspection Program." Among other things, the GAO found that: FDA databases contain inaccurate information on foreign establishments subject to inspection; FDA inspects relatively few foreign establishments each year to assess the manufacturing of drugs currently marketed in the United States; and FDA’s identification of serious deficiencies has led foreign establishments to take corrective actions, but inspections to determine continued compliance are not always timely. The GAO recommends that FDA improve the data that it uses to manage its foreign inspection program, conduct more inspections of foreign establishments, and ensure more timely inspection of foreign establishments where FDA has identified serious deficiencies. HHS agreed that FDA should conduct more foreign inspections, and discussed other FDA oversight initiatives, such as database improvements.
Regulatory and legislative developments posted on Health Industry Washington Watch include:
This post was written by Kevin M. Madagan.
FDA has repeatedly stated over the past year that more enforcement activity in the promotional arena is likely. It appears that time has arrived. Half of FDA’s Division for Drug Marketing, Advertising, and Communications’ (“DDMAC”) citations for misleading advertisements in 2008 were sent in September and October. The citations address typical misbranding issues such as failing to adequately disclose risks, overstating efficacy, broadening indications, and asserting unsubstantiated superiority claims. Whether these citations are the result of DDMAC’s increased budget and new hires, or a continued interest by Congress and the Department of Justice over drug industry promotional issues, one thing appears clear: a new era of increased scrutiny is likely here.
A particularly interesting position that DDMAC has taken in a few of the September and October letters concerns descriptions of disorders and the consequences of failing to obtain treatment. For example, in five letters targeting drugs indicated to treat attention deficit hyperactivity disorder (“ADHD”), DDMAC cites marketing materials that list the difficulties and consequences of untreated ADHD (e.g., poor social-emotional development and job success, inability to complete schooling, illegal behaviors, contraction of sexually transmitted diseases, motor vehicle accidents, and physical injury). In each letter, DDMAC takes the position that listing such difficulties and consequences in association with an ADHD drug constitutes an implied claim that the drug will have a positive impact on these issues. If deemed an implied claim, DDMAC requires studies with endpoints that support each claim.
This is similar to DDMAC’s position on quality-of-life (“QOL”) claims, with health-related QOL claims requiring substantial supporting evidence in the form of adequate and well-controlled studies designed to specifically assess these outcomes.
While the need to have adequate studies to support claims is nothing new, drug manufacturers should remain cognizant of everything listed in marketing materials, including statements concerning the difficulties and consequences of untreated disorders, diseases, or conditions. Drug manufacturers wishing to include such statements must ensure that all implied claims arising from these general statements are supported by substantial evidence (i.e., adequate and well-controlled studies with endpoints targeting each implied claim/impact). Stated otherwise, drug manufacturers must design specific study endpoints to support a disease state description, or must carefully tailor disease state descriptions to pre-existing specific study endpoints.
The Oct. 13, 2008, Pink Sheet provides further detail about DDMAC’s increased activity. DDMAC’s 2008 warning letters can be accessed at fda.gov.
On September 17, 2008, the House Energy and Commerce Committee unanimously approved more than 7 health policy bills addressing such issues as FDA drug and device approvals, internet pharmacy regulation, health care workforce issues, insurance coverage, and medical treatment, including:
The legislation now moves to the full House for further consideration.
This post was written by Catherine A. Durkin and Areta L. Kupchyk.
On May 22, 2008, the Food and Drug Administration (“FDA”) announced plans for what it is calling the “Sentinel System”—a new, national electronic health information surveillance system to track the performance and safety of medical products once they are on the market. See FDA, “The Sentinel Initiative: National Strategy for Monitoring Medical Product Safety” (May 2008). In addition to a whitepaper on the Sentinel Initiative, FDA has published a “Questions and Answers” document, a fact sheet, and information for the consumer that are all available at fda.gov.
The same day, the Centers for Medicare & Medicaid Services (“CMS”) announced a final rule allowing it to share prescription drug claims data for the 25 million Medicare Part D enrollees with other government agencies, as well as with “researchers.” Under the rule, shared data will be available for any purpose “deemed necessary and appropriate by the Secretary,” such as analysis, reporting, and public-health purposes, among other things. See 73 Fed. Reg. 30664 (May 28, 2008); CMS Fact Sheet “Medicare Part D Data Regulation” (CMS-4119-F) (May 22, 2008). The rule becomes effective June 27, 2008.
These coinciding initiatives by the two major federal health regulatory agencies are intended to improve health care quality by using information technology and data mining in new ways. However, numerous policy and strategy questions are still up for debate.
The current system for monitoring drug and device adverse events relies on health professionals and patients to: (1) recognize a potential link between an adverse event and a product; and (2) voluntarily report it, either to the manufacturer or to FDA. In recent years, controversies surrounding certain drug safety issues have contributed to criticisms by members of the public and Congress that the current system is often inadequate. To ensure that FDA would improve its current safety monitoring system, Congress passed legislation in September 2007, the Food and Drug Administration Amendments Act of 2007 (“FDAAA”), Pub. L. No. 110-85 § 905, that required FDA to obtain access to data sources, develop a system to link and analyze product safety data available through these sources, and, using these tools, establish an “active adverse event surveillance” program. The Sentinel System, as its name suggests, is intended to accomplish these goals.
As proposed, the Sentinel System would provide FDA with access to a broad range of publicly and privately maintained health data sources so that FDA could search these sources and gather intelligence on potential safety risks associated with drugs or medical devices as trends emerge. See U.S. Department of Health & Human Services, News Release, New Efforts to Help Improve Medical Products for Patient Safety and Quality of Medical Care (May 22, 2008). Through targeted queries of health information databases (such as the Medicare Part D and other claims databases), FDA claims it would be able to obtain de-identified patient data, perform analyses, and draw conclusions regarding product safety in order to improve the overall quality of medical care. FDA also states that the system would be designed to comply with appropriate security and privacy standards.
The notion that health information technology initiatives (such as electronic health records, e-prescribing, etc.) are the key to improving the quality and reducing the costs of our health care system is a major reason Congress mandated FDA’s expansion of post-approval drug and device surveillance. Although FDA has recognized various efforts (in both the public and private sectors) to collect and make use of electronic safety, performance, and other health/patient data, as listed in the Attachment to FDA’s whitepaper on the Sentinel Initiative entitled “Related Federal/Private Sector Activities,” to date, such efforts have not been coordinated or standardized. The Sentinel Initiative ultimately intends to incorporate these efforts on a national level.
Proposed Mechanics of the Sentinel System
Although FDA is still in the early stages of developing the Sentinel System and specific details are scarce, FDA proposes, at least initially, to capitalize on existing data systems, such as medical claims databases and electronic health record systems, through a “public-private partnership” rather than by creating a new, centralized database. Data sources would continue to be owned and maintained by their current owners. Data owners would either be members of the partnership, or contract with FDA and/or the partnership to provide data. The partnership would be subject to a “defined governance process” and structured according to an “established organizational framework,” both still to be determined. Aside from the Medicare Part D claims database, potential public data sources include Medicare Parts A and B, the Veterans Health Administration, the Department of Defense, and CDC’s National Electronic Injury Surveillance System (“NEISS”).
The multiple data sources would somehow be linked with one another so that they would be interoperable and part of an overall, to-be-developed “information technology architecture.” FDA would thus be able to send queries to a variety of data sources and obtain results quickly, which would be stripped of identifiers to comply with any applicable privacy and security laws and/or standards that protect personal and proprietary information. FDA would then be able to review and analyze the data, observe trends, draw conclusions regarding product safety and performance, and take appropriate measures to address concerns. Accordingly, the system is intended to provide FDA with a stronger, more proactive product safety surveillance capability. The system may also serve as a tool for many other types of research performed by other public health agencies and health researchers; for example, evaluating specific treatment outcomes, or assessing utilization trends.
Open Issues and Next Steps
Based on input from the public during a two-day public workshop FDA held in March 2007 and comment period in early 2007 (see 72 Fed. Reg. 2284 (Jan. 18, 2007)), FDA has identified the following as key issues that must be resolved prior to implementing the Sentinel System:
Although FDA has touched upon some of these issues in its whitepaper and related publications, and has raised numerous others (for example, the scientific credibility of the data analysis and the integrity and independence of the system’s management/governance structure), they remain largely unanswered. The next phase of the Sentinel Initiative will incorporate a series of discussions on the “scientific and policy issues that must be addressed.”
Further, FDA plans to begin meeting with potential partners to formalize specific action items necessary to establish the Sentinel System.
According to the CMS fact sheet on the final Part D claims data rule, CMS will hold an open door forum in June 2008 to review the new rule and discuss the claims data release process, as well as to answer questions from the public. Once this open door forum is scheduled, information will be posted here. If you would like information on how to participate in this open door forum, please contact Katie Durkin at cdurkin@reedsmith.com.
On March 14, 2008, the U.S. Food and Drug Administration (“FDA”) received approval from the U.S. State Department to place eight full-time, permanent FDA employees at U.S. diplomatic posts in the People’s Republic of China, pending authorization from the Chinese government. The FDA will also be hiring five local Chinese nationals to work with the new FDA staff at the U.S. Embassy in Beijing and the U.S. Consulates General in Shanghai and Guangzhou. The FDA expects to be fully staffed in China within 18 months.
In China, the proposed permanent offices are intended to allow the FDA greater access for inspections and increased interactions with manufacturers to help assure products shipped to the United States meet U.S. standards for safety and manufacturing quality. With the opening of an FDA China Office, the FDA’s enforcement arm will more easily extend across the globe and bring some benefits as well as greater challenges for global life sciences companies. The FDA is clearly positioning itself for the demands of the current economy. According to a statement from FDA’s deputy commissioner for International and Special Programs, Murray M. Lumpkin, M.D.:
In an age when a border is not a barrier, the globalized economy demands nothing less than heightened regulatory interoperability, information exchange, and cooperation, especially on product quality and enforcement matters.
The FDA’s “Beyond the Borders” initiative is intended to facilitate the building of stronger cooperative relationships with the FDA’s counterpart agencies around the world, and to enhance technical cooperation with foreign regulators.
Private Sector Responsibility for Import Safety
Although the FDA’s announcement of a permanent presence in China is the latest indication of significant U.S. administrative activity on import safety, ultimate responsibility for product safety and regulatory compliance still generally rests with the private sector manufacturers, importers, distributors, and retailers. The private sector may look to government initiatives for guidance, but must simultaneously employ corporate best practices to contract safely with Chinese manufacturers and suppliers. Such best practices include an appropriate level of due diligence, contract terms that highlight product safety and protect the company, implementation of import compliance procedures, enhanced safety through independent testing, and development of a recall strategy in the event imported products are determined to be unsafe or fail to meet quality standards.
Due Diligence
Proper due diligence must be undertaken with respect to the overseas suppliers or manufacturers. Begin with the basics—know the manufacturer’s name, address, telephone number, fax number and e-mail address. Understand how the manufacturer is incorporated, organized, and registered to do business. Know how the manufacturer is owned—whether it is government-owned, owned by government officials, or otherwise. Understand who owns the manufacturer’s parent company, and the citizenship of any individual owners. Have a handle on the manufacturer’s profile—does it have the expertise and capacity to undertake the work required? Where does the manufacturer bank? Has the manufacturer been involved with any criminal charges, convictions, bankruptcies, or cases of civil litigation in which the company has been a defendant?
Other questions to ask include: What is the manufacturer’s record of and reputation for product safety, plant safety, workers’ rights, and environmental protection? What can be discovered through business references, personal references, and financial references? What information can you obtain from public sources, the local chamber of commerce, the diplomatic corps, from a media search of local and international press accounts, or from lawyers and consultants who are knowledgeable about Chinese manufacturers?
Contracting. As a threshold matter, importers should include clear specifications and safety or quality standards that are to be met by the supplier. The supplier should warrant and certify that it understands and will comply with the applicable specifications or standards. Contracts should include testing procedures and an agreement as to how testing will be accomplished. The contract should include terms about the rejection of non-conforming goods and resulting remedies.
The contact should provide the purchaser with visibility into the supplier’s own supply chain. Importers may insist that the supplier certify facts or make warranties regarding the source of raw materials, manufacturing techniques, or the chain of custody of particular products, such that the manufacturer assumes liability in the event that any of this information is false and the products cause harm.
If intellectual property or know-how is to be exchanged, then the contract should account for and protect those assets. The contract should specify the supplier’s duty to complete the paperwork and assign liability for any failure. The contract may require the inclusion of information required by customs on invoices, such as the date of sale, the identity of the seller, Harmonized Tariff Schedule (“HTS”) classification and valuation of the items, and the port of entry. The contract should require the provision of country-of-origin markings as required.
Child or prisoner labor issues should be verified along with the conditions of general workers’ rights. Environmental degradation possibilities should also be investigated and addressed in contracts. The contract may rightly address local anti-corruption compliance in addition to these other “social” concerns.
An importer should be sure that the Chinese supplier has indemnified it for any harm that may be caused by the products being supplied. This warranty may require the supplier to submit to jurisdiction in the United States for disputes arising under the contract, particularly if the supplier has U.S.-based fixed assets. If the supplier has no fixed assets anywhere other than China, international arbitration is probably preferable to attempting to collect a foreign judgment in China itself.
Import Compliance. In general, it is advisable to have an import compliance program. Such a program should cover overall importation requirements such as shipping, entry, inspection, and related business aspects. An import program should include classification (what is the unique HTS number the product falls under?), appraisal (how much in import duties must be paid based on the tariff rate and value of the imported product?), and country of origin (where does it come from and does it need to be marked “Made in China”?). An import compliance program should address all customer recordkeeping requirements (essentially five years for key documents supporting the entry process). The compliance program should also address what to do in the case of an audit or enforcement action involving customs issues.
Inspections/Audits. An important provision of the written agreement between the parties should allow the importer to have access to the supplier’s or manufacturer’s facility and records for purposes of inspecting the manufacturing operations and evaluating the level of regulatory compliance. Regulatory agencies such as EPA, FDA OSHA, USDA, etc. have broad inspectional authority in the United States. Through memoranda of understandings, certain agencies such as the FDA are allowed to inspect foreign manufacturing sites that produce products or ingredients destined for import into the United States. The reach of these ex-U.S. inspections, although greater with the opening of the FDA office in China, remains much less than in the United States. Allowing a firm’s own employee auditors or third-party auditors retained by a firm to be on-site to observe manufacturing operations and review production records can provide an “early warning” of potential issues to be addressed or avoided.
Product Testing and Systems Evaluation. Product safety and product testing must be an integral part of any supplier or manufacturing contract. This product testing procedure should set forth who will conduct the testing, whether opposite party verification will be available, what party or non-party entity will conduct the testing, and which party will be responsible for payment of testing costs. Parties will need to understand which regulatory industry standards apply, how those standards will be monitored, and how those standards will be extended and enforced though the supplier-sub-prime supplier supply chain—think lead paint on children’s toys.
Importers should consider utilizing “pre-approved” testing facilities such as those identified by National Oceanic Atmospheric Administration and the Consumer Product Safety Commission as identified above. Importers should also consider separate independent testing to be utilized should a level of doubt be raised as to the safety of a particular product or line of products.
In addition to product testing, mechanisms should be put in place, through contract, that allow for the evaluation of the quality control processes extant at the supplier’s operations. This access affords an opportunity to identify potential deficiencies in production, quality control, inspection, and quality assurance/tracking. These mechanisms can be included as part of the provisions allowing for inspections or audits of manufacturers’ facilities.
Recall Strategies. Prudent importers should have a plan in place to minimize the impact of shortcomings in their import safety measurers. That plan should include a recall strategy that addresses the products at issue and the relevant government agencies, such as the CPSC, USDA, and NHTSA, or the FDA. Likewise, the plan should include a tailored approach to address the particular safety risks at issue. The FDA has several levels of recalls that should be addressed—Class I for the recall of products that could cause serious health problems or death, Class II for recall of product that may cause a temporary health problem, and Class III for those recalls involving minor labeling violations. Devising tailored recall plans requires an understanding not only of the company’s supply chain, but also of its distribution chain, and might rightly even include discussions with cognizant governmental recall officials prior to any recall event occurring.
Reed Smith’s Life Sciences Practice In China
Through its offices in Hong Kong and Beijing, Reed Smith represents many life sciences clients regarding their activities in China. From pharmaceutical and medical device companies to distributors, hospitals and physicians, Reed Smith’s lawyers in China advise on foreign direct investment, corporate organization, business operations, securities, protection of intellectual property, technology transfer, mergers and acquisitions, drug registration, product registration, distribution, clinical testing, regulatory compliance, regulatory approval, employment, and dispute resolution. Two members of Reed Smith’s life sciences team in China are dual-qualified physicians and lawyers.
Chris Howse heads up Reed Smith’s leading medical/product liability practice in Hong Kong, advising doctors, hospitals, device and pharmaceutical companies in matters involving the Medical Council, and in civil and criminal litigation disputes.
Hugh Scogin has been based in Beijing for 20 years and is recognized as one of the foremost authorities on Chinese law in the United States, having taught at leading law schools including Yale Law School and New York University School of Law. Hugh’s clients include medical device and diagnostic product manufacturers, and he advises on numerous China-related medical device issues, mergers & acquisitions, foreign direct investment, technology transfer, business operations, securities, and employment and dispute resolution.
This post was written by Areta L. Kupchyk, James M. Wood, Joseph W. Metro, and Kevin M. Madagan.
On February 15, 2008, a year-and-a-half after the sunset of the statute (Section 401 of the Food and Drug Administration Modernization Act) intended to permit the dissemination of medical literature about unapproved uses of drugs and medical devices, the Food and Drug Administration (“FDA”) proposed a draft guideline for such dissemination. Often referred to as “the distribution of off-label use journal articles,” FDA has saddled the proposed guidelines with a much heftier title: “Guidance For Industry: Good Reprint Practices for the Distribution of Medical Journal Articles and Medical Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices.”
The FDA has invited comments—which must be submitted no later than April 14, 2008—on the draft guidance. Only after consideration of any comments will FDA move to finalize the draft guidance.
The draft succinctly details the background of efforts to regulate distribution of literature about unapproved uses, noting the need to balance the law’s prohibition on distributing or promoting “unapproved uses of approved drugs and approved or cleared medical devices” with the “important public policy” of providing information that “may even constitute a medically recognized standard of care.” FDA concludes that the touchstone for lawful dissemination of literature about unapproved uses is that the publications “are truthful and non-misleading.”
To meet this standard, FDA proposes “principles of Good Reprint Practices” that include criteria for determining the type of publication, and the manner in which the publication can be distributed.
Criteria for Types of Publications
FDA proposes four criteria for qualifying a journal article for dissemination by a manufacturer (which includes any person licensed to distribute or market the product):
FDA also proposes distribution and publication guidelines to ensure that drug and device manufacturers (without recognizing any distinction between the commercialization practices of a drug and device manufacturer) do not improperly promote an off-label use. The article should:
It appears here that a manufacturer may fund an article so long as it does not “significantly influence” the writing of the article. The guidelines would also not bar a person with a financial interest from having any influence over the article, but only significant influence.
In the draft, FDA also reminds the reader that the article must not pose a significant risk to public health or be false or misleading. In other words, these prohibitions are not recommendations but rather requirements. FDA defines false or misleading by giving three examples:
If this draft guidance is implemented as written, FDA would consider certain types of articles not appropriate for distribution by a manufacturer, regardless of content, and even if the content is truthful and not misleading. These include:
How Publications Can Be Disseminated
The second major section of the draft guidance describes what FDA would consider to be an acceptable manner of dissemination, and recommends that a disclosure statement be prominent and permanently affixed.
As to the form of the publication, the basic criteria are that the article be:
The publication must also be “accompanied by”:
These criteria appear particularly burdensome for manufacturers and fail to include the same criteria FDA proposes above for qualifying articles for dissemination. FDA does not appear to expect that any contrary articles be credible, subject to peer-review, be published by an organization with an editorial board, and based on adequate and well-controlled studies. Under this draft guidance, it is conceivable that a letter to the editor or an article funded by a competitor might need to accompany an article distributed by a manufacturer.
In addition, these criteria do not acknowledge differences between devices and drugs. For example, an instruction of use (“IFU”) manual for a medical device might already be in the possession of the physician who uses the device and, because of its length and size, may be burdensome to provide with each reprint. It is also not clear whether the term “accompany” would require any physical attachment to the article or how closely the labeling should be to the qualified article. The same term is used in the definition of labeling (“all labels and any written, printed or graphic matter accompanying a container or wrapper”). In that context, the Supreme Court ruled that “labeling” did not need to be physically attached to the product so long as its content supplements or explains the use of the product, and the textual relationship is significant. Kordel v. U.S., 335 U.S. 345 (1948). Consistent with this definition of accompanying, FDA’s expectation could be met if the labeling (including an IFU), along with relevant bibliographies, would be provided at least once before the article is provided.
To further ensure that the publication is not used to “promote” the product, FDA would expect that a manufacturer provide it “independently” from any other promotional material for the product. In addition, FDA would expect that articles generally not “be distributed in promotional exhibit halls or during promotional speakers’ programs.” Interestingly, implicit in this guideline, it would be appropriate, therefore, for a manufacturer to set up a booth solely for the dissemination of qualifying articles inside conference areas rather than in separated exhibition halls. This would be consistent with FDA’s expectation that promotional material be kept separate from educational and scientific materials.
Finally, notwithstanding that FDA expects an article not to be marked or highlighted, FDA proposes that the manufacturer provide a disclosure statement that is “prominently displayed and permanently affixed.” The disclosure should include all of the following information:
Here, FDA’s proposed disclosure statement provides an unnecessary redundancy and is unnecessarily burdensome. For example, any financial interest of the authors would have already been disclosed or addressed by the disclosure policy of the editorial board of the publishing organization, as FDA specifies in the first part of the guidance.
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