FDA Announces Review of Bar Code Final Rule

This post was written by Erin Janssen.

The Food and Drug Administration (FDA) has published a notice announcing that it will conduct a review of its 2004 ‘‘Bar Code Final Rule,” which requires certain human drug products and biological products to have a bar code. The rule was intended to help reduce the number of medication errors that occur in hospitals and other health care settings FDA now wishes to reassess the costs and benefits of the rule and to identify any relevant changes in technology that have occurred since it went into effect. FDA will use the information received to assess whether the Bar Code Final Rule is achieving its intended benefits as effectively as possible or should be modified. Initial comments must be received by January 9, 2012 and reply comments by February 23, 2012. 

President Issues Executive Order Regarding Drug Shortages

This post was written by Erin Janssen.

On October 31, 2011, President Obama signed an Executive Order directing the FDA to take action to help further prevent and reduce prescription drug shortages, protect consumers, and prevent price gouging. The President’s order directs FDA to broaden reporting of potential shortages of certain prescription drugs and to further expedite regulatory reviews that can help prevent or respond to shortages. Under this policy, FDA also will work with the Department of Justice, which will examine whether potential shortages have led to illegal price gouging or stockpiling of life-saving medications. The FDA has compiled information about its actions to address drug shortages

FDA Proposes Amendments to Orphan Drug Rules

The Food and Drug Administration (FDA) published a proposed rule on October 19, 2011 that would amend the 1992 Orphan Drug Regulations that implement the Orphan Drug Act. The amendments proposed are “intended to assist sponsors who are seeking and who have obtained orphan drug designation of their drugs, as well as FDA in administering the orphan drug program.” The FDA will accept comments on the proposed rule until January 17, 2012. Reed Smith has prepared a client alert summarizing the proposed rule and discussing the potential impact of the proposal on the drug, biological product, and biotechnology industries. To read the full alert, click here.

FDA Issues Final Guidance on Risk Labeling for Prescription Drugs and Biological Products

This post was written by Erin Janssen and Areta Kupchyk

On October 12, 2011 the FDA announced the availability of guidance for the industry entitled Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products--Content and Format.” This guidance is intended to assist applicants and reviewers in drafting the “Warnings and Precautions, Contraindications, and Boxed Warning” sections of labeling for human prescription drug and biological products. The recommendations in the guidance are designed to ensure that the labeling is clear, useful, informative, and to the extent possible, consistent in content and format. The guidance provides recommendations on how to determine which adverse reactions are significant enough to warrant inclusion in the "Warnings And Precautions" section; how to decide what situations warrant a "Contraindication," and when to include a "Boxed Warning." The guidance also provides recommendations on how to organize each section and what information to include when describing warnings and precautions, in situations when the use of the product is contraindicated, and in a boxed warning.

FDA Guidance on Reproductive and Developmental Toxicities

This post was written by Erin Janssen and Areta Kupchyk.

On September 23, 2011, FDA released guidance entitled Reproductive and Developmental Toxicities--Integrating Study Results to Assess Concerns.” The guidance describes an approach to estimating possible human developmental or reproductive risks associated with drug or biological product exposure when a finding of toxicity has been identified, but definitive human data are unavailable. The guidance is intended for drug developers intending to submit NDAs and BLAs, and who are assessing nonclinical toxicity information. The recommendations included will also help to ensure a consistent review of reproductive and developmental toxicity data among Center for Drug Evaluation and Research review staff.

The guidance does not: (1) give detailed advice about labeling or placement of toxicity information in product labeling (for information on labeling, see 21 CFR 201.57); or (2) discuss clinical data, the integration of nonclinical and clinical data, or the clinical implications of these data. The approach presented in the guidance for assessing nonclinical reproductive and developmental toxicity data involves the integration and careful consideration of a variety of different types of nonclinical information: Reproductive toxicology; general toxicology; and toxicokinetic and pharmacokinetic information, including absorption, distribution, metabolism, and elimination findings. The approach is used when there is a toxicity finding and focuses on assessing the likelihood that a drug will increase the risk of adverse human developmental or reproductive outcomes. The approach includes noting when studies were not conducted or when they were not performed using relevant model systems or at appropriate dose ranges.

FDA released a prior draft of this guidance in 2001, however, one important change has been made. The description of a process that involved assignment of values of +1, -1 or 0 to the various factors was removed from the guidance. Comments on the guidance may be submitted at any time.

FDA Proposed Rule to Amend Sterility Test Requirements for Biologicals

This post was written by Erin A. Janssen.

On June 21, 2011, the Food and Drug Administration (FDA) published a proposed rule that would amend current sterility test requirements for biological products to provide manufacturers with greater flexibility and to encourage use of the most appropriate and state-of-the-art test methods for assuring the safety of biologicals. Comments on the proposed rule are due by September 19, 2011. The most significant proposed changes to current regulations governing sterility testing include the following: (i) elimination of specified sterility test methods, culture media formulae, and culture media test requirements; (ii) elimination of specified membrane filtration procedure requirement for certain products; (iii) elimination of specified sterility test requirements for most bulk material; (iv) modification of the repeat sterility test requirements (repeat tests would occur only once for each lot and would be limited to situations where the quality control unit conclusively determines that the contamination is the result of laboratory error or faulty materials used in conducting the sterility test); (v) replacement of the storage and maintenance requirements for cultures of test organisms used to determine the ‘‘growth-promoting qualities’’ of culture media with (a) validation requirements specifying that any sterility test used is able to consistently detect the presence of viable contaminating microorganisms and (b) verification of “growth-promoting properties” or microorganism-detection capabilities of test and test components; (vi) replacement of the sample size or amount requirement with a requirement that the sample be appropriate to the material being tested; and (vii) replacement of the current “Interpretation of test results" paragraph under § 610.12(c) with a requirement that manufacturers establish, implement, and follow written procedures for sterility testing that describe, at a minimum, the test method used, the method of sampling, and the written specifications for acceptance or rejection of each lot. FDA is specifically seeking public comment on whether the phrase "growth-promoting properties," rather than "growth-promoting qualities" is more appropriate terminology within the regulations. FDA also requests comments on whether the proposed testing validation requirements are sufficient to ensure adequate validation of novel sterility test methods, whether the current exceptions to the sterility test requirement should be changed, and the frequency with which manufacturers diverge from the retesting protocol and the costs that limiting retests will impose. 

President Obama Outlines Plans for Deficit Reduction/Entitlement Reform

On April 13, 2011, President Obama delivered a speech outlining his plan for reducing the federal budget deficit by $4 trillion within 12 years, in part through Medicare and Medicaid reforms. Specifically, the President is calling for $480 billion in Medicare and Medicaid cuts by 2023 and at least an additional $1 trillion in cuts over the subsequent decade. One mechanism the President proposes to control Medicare spending is directing the Affordable Care Act’s (ACA) Independent Payment Advisory Board (IPAB) to hold Medicare cost growth per beneficiary to the gross domestic product per capita plus 0.5 percent (rather than 1.0 percent under the ACA) beginning in 2018. If spending growth exceeds the target, the IPAB's proposals go into effect automatically unless Congress enacts alternative legislation to achieve required savings. The President proposes additional budget enforcement measures to ensure savings targets are met. The President also calls for $200 billion in cuts in Medicare prescription drug spending (including by "leveraging Medicare’s purchasing power," speeding the availability of generic biologics, and prohibiting brand-name companies from entering into “pay for delay” agreements with generic companies). With regard to Medicaid, the plan calls for savings of at least $100 billion over 10 years. According to the summary, the President’s plan would replace the current federal matching formulas with a single matching rate that rewards states for efficiency and automatically increases if a recession increases enrollment and associated state costs. Additional Medicare and Medicaid "accountability" proposals include, among others: restricting states’ use of provider taxes to lower their state spending without providing additional health services; recovering "erroneous" payments from Medicare Advantage plans; capping Medicaid payments for durable medical equipment (DME); and implementing Medicaid management of high prescribers and users of prescription drugs, among other things.  President Obama also announced that he has asked Majority Leader Reid, Speaker Boehner, Minority Leader Pelosi and Minority Leader McConnell to each designate four members to participate in bipartisan, bicameral negotiations led by the Vice President, beginning in early May to develop a legislative framework for comprehensive deficit reduction.

President Obama’s deficit reduction proposal comes at a time when the House of Representatives is considering a budget proposal for FY 2012 (H. Con. Res. 34) drafted by House Budget Chairman Paul Ryan (R-WI) that calls for $6.2 trillion in spending cuts over the next 10 years, although estimates of savings vary (see http://budget.house.gov/fy2012budget/). Among other things, the budget resolution includes significant structural reforms of the Medicare and Medicaid program and repeal of the ACA. With regard to Medicare, the plan would convert the Medicare program to a premium support model for individuals becoming eligible for Medicare beginning in 2022. Under this policy, traditional Medicare eventually would be replaced with a system whereby beneficiaries would choose among competing health plans meeting coverage standards (similar to current Medicare Part C plans), and a premium-support payment would be made to the plan, subsidizing its cost, with increased assistance provided to lower-income beneficiaries and those with greater health risks. The resolution also would convert federal Medicaid spending into a block grant program. In addition, the measure generally calls for repeal of the ACA, although presumably such efforts would focus on ACA insurance-related provisions rather than, for example, the extensive Medicare provider reimbursement or fraud enforcement provisions. The House Budget Committee approved the measure on a party-line vote, and it is scheduled to be considered by the full House this week. Note that the budget resolution simply provides the spending and revenue instructions for the Congressional committees; enacting legislation would need to be adopted to implement any of the proposed policy changes. Democratic leaders have widely criticized the Ryan plan. Nevertheless, particularly in light of today’s proposal by the President, it appears increasingly likely that some form of entitlement reform may advance this year.

FDA Releases Guidance Document on Process Validation

This post was written by Paul Sheives.

FDA has issued a final guidance document entitled “Process Validation: General Principles and Practices,” which replaces FDA’s 1987 “Guideline on General Principles of Process Validation.” The guidance is intended to outline the general principles and appropriate elements of process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (APIs or drug substances). The guidance seeks to meld process validation with the product life cycle concept, which links product and process development, qualification of the commercial manufacturing process, and maintenance of the process in a state of control during routine commercial production. The document addresses the three stages of process validation (process design, process qualification, and continued process verification), concurrent release of process performance qualification batches, documentation, and analytical methodology.

Memorandum of Understanding Between FDA and CMS

This post was written by Paul Sheives and Areta Kupchyk.

The FDA and CMS have entered into a Memorandum of Understanding (MOU), effective June 25, 2010, to promote collaboration and enhance knowledge and efficiency by sharing information and expertise. In particular, the MOU highlights the agencies’ “common needs for evaluating the safety, efficacy, utilization, coverage, payment, and clinical benefit of drugs, biologics, and medical devices.” Included among the action items in the MOU are the appointment of a liaison for each agency, the establishment of a joint agency meeting to discuss implementing the MOU, an agreement to set reasonable expectations on responses to requests for information, and the implementation of certain safeguards to protect the transmittal and use of trade secret and confidential information. 
 

FDA Meeting on Risk Evaluation and Mitigation Strategies (July 27-28)

This post was written by Paul Sheives.

FDA will hold a 2-day public meeting on July 27 and 28, 2010 to address the development and implementation of risk evaluation and mitigation strategies (REMS) for drugs and biological products. The purpose of the meeting is to seek public input on various concerns that stakeholders have raised on the impact of REMS throughout the health care system. Registration for the meeting closes July 6, 2010. FDA also seeks input on the draft guidance entitled ‘‘Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications’’ (released in October, 2009). The comment period for the draft guidance has been reopened; FDA will accept comments until August 31, 2010. 

FDA to Post New On-line Information Regarding Safety Monitoring Issues for Recently-Approved Drugs and Biologics

This post was written by Paul Sheives.

FDA announced a new initiative, required under the Food and Drug Administration Amendments Act of 2007, to post summaries of FDA safety analyses and the agency’s plan to address them on the FDA website. Because evidence of some side effects arises following approval of the products, FDA is posting this information as a resource for consumers and health care professionals. The safety information posted on the website is pulled from reports to the FDA’s Adverse Event Reporting System and the Vaccine Adverse Event Reporting System, periodic safety reports by manufacturer, reports in the medical literature, and data from ongoing post-marketing studies. FDA will begin preparing summary reports for drugs and biologics approved since September, 2007.
 

FDA Review of Articles for Treatment of Rare Diseases

FDA is hosting a meeting June 29 and 30 on FDA Review and Regulation of Articles for the Treatment of Rare Diseases.” The hearing is intended to provide stakeholders, including the pharmaceutical industry, with an opportunity to present their views on the way FDA regulates the scientific evaluation of, marketing authorization for, and postmarket surveillance of, articles pertaining to drugs, biological products, and devices used for rare diseases. Written comments on this topic also will be accepted. 

CMS Transmittals on Discarded, Self-Administered Drugs/Biologicals

CMS has issued a Medicare Claims Processing Manual update regarding discarded drugs and biologicals, including language regarding use of the JW modifier (“Drug or Biological Amount Discarded/Not Administered to Any Patient”). The manual update is effective July 30, 2010. In addition, CMS has updated its manual language relating to Determining Self Administration of Drug or Biological. Due to recent drugs approved for marketing by the FDA, CMS is allowing other routes of administration besides injections (e.g., oral drugs, suppositories, topical medications) to be considered not-usually self administered, effective July 30, 2010. 

Proposed Rule Amending Informed Consent Disclosure

This post was written by Paul Sheives.

On December 29, 2009, the Food & Drug Administration Act (FDA) issued a proposed rule that would amend the informed consent regulations to require the addition of an element regarding disclosure of information to the National Institute of Health (NIH) clinical trials database. Under the Food and Drug Administration Amendments Act of 2007, sponsors of “applicable clinical trials” are required to submit information for listing in the NIH clinical trial database. The proposed rule would require all informed consents for such “applicable clinical trials” – including specified drug, biologic, and device clinical investigations -- to include language informing the subject of the potential disclosure of the de-identified data to the clinical trials database (www.clinicaltrials.gov). FDA is accepting comments on the proposal until March 1, 2010.