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“Paperless Labeling Rule”
Proposed Rule First LookJanuary 2015
Comment Period
• Full Title: Electronic Distribution of Prescribing Information for Human Prescription Drugs, Including Biological Products
• Issued 18-Dec-2014• Comment Period ends 18-Mar-2015• Comments to http://www.regulations.gov or
to Division of Dockets Management
Locator Information
• Action: Proposed rule.• Document Citation:79 FR 75506• Page: 75506 -75527 (22 pages) • CFR:21 CFR 201; 21 CFR 606; 21 CFR 610• Agency/Docket Number: Docket No. FDA-2007-N-0363• RIN:0910-AG18• Document Number:2014-29522• Shorter URL https://federalregister.gov/a/2014-29522• PDF: http://
www.gpo.gov/fdsys/pkg/FR-2014-12-18/pdf/2014-29522.pdf
FDA has Authority to Require
• that the prescribing information be distributed electronically, rather than by the shipment of a paper copy of the prescribing information with each container of a prescription drug. [section 501(f)(1) of the FD&C Act]
• That the prescribing information no longer physically accompany the product in paper form, except as provided in the exempting provisions
• That the label will bear a statement that includes– the FDA labeling repository Web site address – toll-free telephone number for alternate access to prescribing
information
History (What? SPL?)• December 11, 2003: Amended regulations governing the format in which certain labeling is required to be
submitted for review with NDAs, ANDAs, certain BLAs, supplements, and annual reports (68 FR 69009). The final rule required the electronic submission of certain prescribing information in a form that FDA can process, review, and archive. This action was taken to simplify the labeling review process and to provide more timely approval of labeling changes.
• Guidance to support this requirement (April 2005) entitled “Providing Regulatory Submissions in Electronic Format—Content of Labeling” (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072331.pdf). This guidance describes the Structured Product Labeling (SPL) standard, which is based on extensible markup language (XML), as the most up-to-date electronic format that FDA can use to process, review, and archive prescribing information, and other labeling changes that are submitted electronically as part of a regulatory submission.
• In 2007, Congress enacted the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85) (FDAAA). Section 224 of FDAAA, which amends section 510(p) of the FD&C Act (21 U.S.C. 360(p)), expressly requires owners and operators of establishments engaged in the manufacture of drugs (manufacturers [3] ) to submit drug establishment registration and drug listing information electronically
• FDA guidance (May 28, 2009) , entitled “Providing Regulatory Submissions in Electronic Format—Drug Establishment Registration and Drug Listing” (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072339.pdf). recommendations to manufacturers on how to create and submit separate electronic SPL files containing drug establishment registration and drug listing information, including a copy of the required components of labeling, for each marketed prescription human drug, including biological products covered by part 207.
• The FD&C Act currently requires manufacturers to update the drug listing information (which includes the product labeling) at least twice a year, in June and December, if there have been changes to the listing elements in the prior 6 months (21 U.S.C. 360(j)(2)).
Major Provisions• Distribute prescribing information electronically, instead of in
paper form. – Submit prescribing information every time there is a change to the
labeling.– Review labeling posted at FDA’s web site to verify that the correct
version appears – Notify FDA if correct version is not posted
• Product’s Immediate Container Label and Outside package to bear a statement directing HCPs to FDA’s labeling repository [21 CFR 201.100(b)(8), 21 CFR 610.61(t)]– Partial label rule still available
• Possibility of exemption – requested by manufacturer or directed by FDA
Associated Initiatives
• Electronic prescribing provisions of Medicare Prescription Drug Improvement and Modernization Act (Pub. L. 108-173)
• Requirement for bar codes on certain drug labels• Requirement for Submission of Electronic
Labeling in Product Approval Applications• Electronic Registration of Drug Establishments
and Listing of Drug Projects• “DailyMed” initiative with NLM
Patient Labeling Not in Scope – for Now
• FDA-approved information intended for patient use, patient package inserts, Medication Guides
• Covered by different initiative by FDA• Will continue to be provided in paper form• Electronic submission to FDA with prescribing
information
New
• Blood & Blood Components intended for transfusion (21 CFR part 607)
• Compliance date not detailed in Proposed Rule
Paper may still be needed?
• Public Health Emergency, Natural Disaster or Other Situation involving Field Response– Emergency Use Authorization (21 USC 360 bbb-3)
• Resource Constraints or Geographic Location – Some rural areas have limited Internet access
• Export for Humanitarian Use in Other Countries
Implementation Timeline(if/when Final Rule is issued)
• Effective date of 6 months after publication of final rule in Federal Register
• Compliance date of 2 years after publication of final rule
Start-up Actions
• FDA populates labeling repository (labels.fda.gov) with labeling that has already been electronically submitted to FDA to comply with current requirement.
• Manufacturers must review current prescribing information in the repository
Proposed Label Statements
• Immediate Container Label and Outside package to bear a statement directing HCPs to FDA’s labeling repository [21 CFR 201.100(b)(8), 21 CFR 610.61(t)]
• Biological product containers capable of bearing a full label [21 CFR 610.60(a)(8)]– Partial label rule not changed [21 CFR 610.60(c), (d)]
• Blood and blood components container label statement [21 CFR 606.121(c)]
• Current, fully-functional toll-free # to obtain current prescribing information [CFR 201.100(c)(5)]
• Distribution of prescribing information electronically [21 CFR 201.100(c)(3)]
Exemptions [201.100(g)]
• Manufacturer’s request to FDA must– Describe reasons that compliance with the electronic
distribution of prescribing information requirements • could adversely affect the safety, effectiveness, purity or
potency of the drug;• Is not technologically feasible; or• Is otherwise inappropriate; AND
– Explain the concerns underlying the request could not reasonably be addressed by other measures
• FDA – on its own initiative -- can also exempt a drug from the requirement
Submission of Labeling [201.100(c)(4)]
‘in a format that FDA can process, review, and archive for distribution via the FDA’s labeling repository Website’– i.e., SPL to be posted on labels.fda.gov
• Newly approved drugs: NDA, BLA, ANDA applicants submit prescribing information in time for the prescribing information to be posted in the labeling repository before the drug enters interstate commerce .
Proposed Submission Requirements
• Already approved drugs: most current labeling to FDA each time the prescribing information is changed, including those changes submitted as supplements or in an Annual Report [314.70 and 601.12]
Submission Requirements - More
• Prior Approval Supplement: w/in 2 business days following FDA approval of the supplement
• CBE Supplement: same business day as supplement submission• Manufacturers that are not Applicants (e.g., Repackers): w/in 2
business days of the posting of the applicant’s updated labeling• Unapproved drugs: w/in 2 business days of a change to the
labeling.• ANDAs: Should a conforming amendment cross-referencing
201.100 be added to 314.97 [Submission of changes to an abbreviated application]
Submission Requirements - More
• Drug Listings:IF a supplemental change is submitted under proposed 201.100(c)(4) before the required submission for updating registration/listing (207) AND
• There is no additional change to the label between the time of the submission and the time of the drug listing/registration, THEN
• Labeling information would not need to be submitted again with drug listing/registration
Post-Submission
• FDA: Prescribing information will be posted on next business day following the date of submission.
• Manufacturer responsible for verification that– Labeling is posted to fda.labels.gov w/in 2
business days of submission– Labeling on repository is the correct labeling
Issues & ReportingIssue Timing Action
Correct prescribing information is not posted on public repository w/in 2 business days of submission
w/in 4 business days of submission to FDA labeling repository
Contact SPL Coordinator* @[email protected]
*Include information such as NDC code, drug name, description of problem with the labeling
Incorrect prescribing information is posted on public repository
w/in 2 business days of submission to FDA labeling repository
Outdated labeling posted on the labeling repository renders a product misbranded; Applicant or manufacturer may be subject to enforcement action by
the Agency
Promotional Labeling [201.100(d)(4)]
• Continue to disseminate with a copy of FDA-approved product labeling in paper form.
Benefits of electronic distribution
1. The provision of adequate directions for use to persons prescribing, dispensing, and administering the drug;
2. The provision of adequate warnings to prescribers against use in patients where a drug’s use may be dangerous to health; &
3. The prevention of unsafe prescribing of prescription drugs
Proposed Changes to • 21 CFR Part 201
(Drugs; Labeling; Reporting and recordkeeping requirements)– 201.100 (b), (c)(1), (c)(3), (c)(4), (c)(5), (d) , (d)(2), (d)(4)-new (g)– 201.306– 201.310
• 21 CFR Part 606 (Blood; Labeling; Laboratories; Reporting and recordkeeping requirements)– 606.121– 606.122
• 21 CFR Part 610 (Biologics; Labeling; Reporting and recordkeeping requirements)– 610.60– 610.61(k) and (n)
What’s Next?
Estimates of Reporting Burden
