Regulatory Process & Cycle

Transcription

1 Regulatory Process & Cycle Menu Review regulatory process Example -- Examine pediatric labeling Pharm 532 April 1, 2009 Discuss project topics 1 2 Objectives understand... civics 101 branches of government, evolution of law, regulations, status of guidelines how to reverse engineer a regulatory document legal origins efficiency tricks The Law (code regulations) 21 USC 301 (the Act ); 42 USC 201 (Public Health Service Act) thou shalt not adulterate misbrand penalties -- civil and criminal 21 CFR proposed rule (NOPR) in Federal Register; comments final rule in FR with effective date; importance of preamble browse feature for FR 3 4

2 FD&C Act Definitions iti Drug Device LabelingL b New drug FD&C Act Prohibited Acts & Penalties Misbrand Adulterate Administrative i ti Penalties Clinical hold Refuse to file Debarment Disgorgement Injunction Seizure Revocation of approval / license / market clearance 5 6 Regulatory Cycle A Basic Policy Analysis Process from Patton & Sawicki Basic Methods of Policy Analysis and Planning, 2nd Edition, Verify, Define, and Detail the Problem 6. Monitor the Implemented Policy 2. Establish Evaluation Criteria 5. Display and Distinguish among Alternative Policies 3. Identify Alternative Policies 7 4. Evaluate Alternative Policies 8

3 Bardach: Eightfold Path Regulatory Process 1. Define the problem 2. Assemble some evidence 3. Construct the alternatives 4. Select the criteria 5. Project the outcomes 6. Confront the tradeoffs 7. Decide 8. Tell your story Legislative creates Administrative enforces Judicial interprets t Congress passes law; president signs Agency "promulgates" regulation; "final rule" in FR Agency may develop "guidelines" comments from affected parties 9 10 Regulatory Boundaries Constitutional First Amendment free speech Tenth Amendment states rights preemption Administrative Procedures Act Across federal agencies; Title 5 USC; individual agencies Individual states Like cricket, rules confusing/boring; got to know them if you want to win Pediatric i Rule Problem 38 Act required demonstration of safety, but didn t specify which populations <25% of drugs used in children have been evaluated for safety or efficacy Increase in pediatric exposure Two-fold reluctance for pediatric testing Kids and their agents don t want the risk Manufacturers don t want risk or additional expense; stuff sells itself Harriet Lane, etc. 11 Steinbrook R Testing medications in children. NEJM 2002; 347 (18):

4 What s a pediatric i Newborn 1m 2y Child 2 12y Adolescent l t 12 16y16 What are the issues? What about the elderly? Pediatric i issues Science Availability, distribution, disposition SE peculiar to pediatrics Ethics IRB risk/benefit assessments Consent issues: who benefits? Compensation for risk: who benefits? Practical Subject availability Policy Evolution Policy Evolution 2 Date Event Date Event 1979 FDA establishes a section for drug labels about pediatric use 1994 FDA requires manufactures to determine if there is sufficient data to support pediatric labeling; voluntary collection of data 1997 FDAMA 6-month exclusivity; sunset provision; NOPR for pediatric rule requiring manufacturers to assess safety & effectiveness in specified circumstances 2000 FDA mandates compliance with pediatric rule submission of pediatric studies. Challenged in federal court Children s Health Act; reauthorizes 6-month exclusivity 2001 FDA promulgates regulations specifying additional safeguards for clinical research involving children 1998 final rule published for pediatric rule ; effective April /2002 Best Pharmaceuticals for Children Act; reauthorizes 6-month exclusivity through 2007; NIH mandate to obtain information about 16 off-patent drugs or patented drugs manufacturers don t want to study

5 Policy Evolution 3 Date Event 3,4/2002 DC court finds for the plaintiffs; HHS announces that it won t, then will continue to enforce pediatric rule 4&5/2002 S2394; HR4730;...S650 Under the Pediatric Rule, approval actions taken or applications submitted on or after April 1, 1999, for changes in active ingredient, indication, dosage form, dosing regimen, or route of administration were required to include pediatric assessments for indications for which sponsors were receiving or seeking approval in adults, unless the requirement was waived or deferred. Note on codification numbering: S650 Pediatric Research Equity Act of 2003 Amends FD&C at Sec 505B (21USC351) 17 More on Final Rule Stylized Structure Summary Effective Date; compliance date Further information Supplementary Information Introduction Highlights Comments on proposed rule Legal authority Implementation plan Paperwork Reduction Act (reporting burden) Environmental Impact Analysis of Impacts Number of affected products and required studies Number of patients Cost of compliance Studies Formulations Added paperwork Benefits Regulatory Alternatives Codified language 18 Summary Effective Date; Compliance Date The Food and Drug Administration (FDA) is issuing new regulations requiring pediatric studies of certain new and marketed drug and biological products. Most drugs and biologics have not been adequately tested in the pediatric subpopulation. As a result, product labeling frequently fails to provide directions for safe and effective use in pediatric patients. This rule will partially address the lack of pediatric use information by requiring that manufacturers of certain products provide sufficient data and information to support directions for pediatric use for the claimed indications. DATES: Effective date. The regulation is effective April 1, Compliance dates. Manufacturers must submit any required assessments of pediatric safety and effectiveness 20 months after the effective date of the rule, unless the assessments are waived or deferred by FDA

6 Supplementary Information NOPR 62FR43900 ( the proposal ) US marketed drugs are inadequately labeled for pediatric subgroups; safety / efficacy Poses significant risk of age-specific ARs unexpected from adult experience Decreased access to new therapies Prior attempts (i.e., 94 rule survey) 94 rule failed to produce much action These data indicate that voluntary efforts have, thus far, not substantially increased the number of products entering the marketplace with adequate pediatric labeling. FDA has therefore concluded that additional steps are necessary to ensure the safety and effectiveness of drug and biological products for pediatric patients. This rule requires the manufacturers of new and marketed drugs and biological products to evaluate the safety and effectiveness of the products in pediatric patients, if the product is likely to be used in a substantial number of pediatric patients or would provide a meaningful therapeutic benefit to pediatric patients over existing treatments. 21 Thus, FDAMA provides no guarantee that the studies conducted d under the statute t t will result in improved pediatric labeling. 22 Scope New chemical entity or new (never-before- approved) biological product new active ingredients new dosage forms new dosing regimens new routes of administration excludes l d orphan drugs already marketed drugs 94 rule Remedies for Violation of Rule injunction misbranded under 502 (21USC352) unapproved new drug under 505(a) (21USC355) unlicensed under 351 Public Health Service Act violation of injunction contempt or other courtordered penalties (fines) rarely withdrawal of approval / license 23 24

7 Comments on Proposed Rule FDA received 54 written comments on the proposed rule from pediatricians, professional societies, parents, members of the pharmaceutical industry, organizations devoted to specific diseases, and patient groups. A significant majority of the comments supported regulations requiring that drugs and biologics be studied in children. Some comments, primarily those from the pharmaceutical industry, opposed a pediatric study requirement, arguing that existing voluntary measures and incentives were sufficient to ensure adequate pediatric labeling. Finally, a number of comments addressed FDA s legal authority to require pediatric testing of drugs and biologics. 25 Comments 2 Day-long public hearing on October 27, 1997, in Washington, DC, at which recognized experts in the field, members of the pharmaceutical industry, and other interested parties were given an opportunity to discuss the issues raised by the proposed rule. There were three panels, each of which comprised representatives from industry, the pediatric community, organizations devoted to specific diseases, patient groups, and a bioethicist. The panels considered the following three issues: 1) When pediatric studies are needed, 2) what types of studies are needed, 3) special challenges in testing pediatric patients. 26 Up-to-date information Resources More Resources FDA listserv from any of the Centers American Health Line Sign up via HealthLinks Kaiser Daily Health Policy Report FDC Reports The Pink Sheet, etc. FDA News Script UW Library services SCLIP (Law) Any journal subscription ISI Web of Science Lexis-Nexis i PubMed Reference Librarians Terry Jankowski (HSL) Government Publications Law Congressional Quarterly (via Lexis-Nexis) Federal Register Via Lexis-Nexis HSL Reference Database Info more Select Lexis-Nexis Academic Legal Reference Federal Regulations (pull down menu) HeinOnline Main Library page Research Databases search for Hein FR library WA Legislature information wa gov WA Public Disclosure Commission Search the Database 27 28

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