Section 804 Importation Program Quality Assurance Tool

Submit proposal to FDA in electronic format via email at SIPDrugImportsandRFP@fda.hhs.gov. 

Tips

• Ensure the proposal includes an overview with all information listed under 251.3(d)(1) – (11).
• FDA recommends organizing the table of contents clearly for navigating all sections and attachments.
• The SIP proposal can include attachments/appendices. Files can be submitted to SIPDrugImportsandRFP@fda.hhs.gov. Ensure files submitted include the ability to search text to ensure efficient review. Large files may need to be broken into separate documents and submitted via multiple emails to FDA.

Tips

• When selecting SIP participants, consider how the SIP sponsor will ensure that all the participants in the SIP comply with statutory and regulatory requirements (251.3(e)(10)) and whether entities or persons are engaged in the type of activity they would perform under the SIP proposal. For example, a repackager/relabeler is likely to already have facilities and capabilities in place to affix or imprint a product identifier based on existing Drug Supply Chain Security Act (DSCSA). Any entity with which the importer contracts to accomplish such labeling must have systems and processes in place to meet applicable DSCSA requirements, even if the entity is not engaged in a repackaging operation of the eligible prescription drug.
• If manufacturers of the finished dosage form or the active ingredient(s) of each eligible prescription drug are not known at the time a SIP proposal is submitted, it is acceptable to omit this information in the SIP proposal. However, this information must be provided in a pre-import request (251.5).

Tips

• Ensure the attestation is signed and information statement addresses each responsible individual, foreign seller and importer
• If the responsible individual(s), foreign seller or importer has not been involved in, or convicted of, any such violations, an attestation must still be provided as part of the SIP proposal.

Tip

• If there are multiple locations for the foreign seller and/or importer, indicate the role of each location.

Tips

• If it is not possible to relabel a product without affecting the container closure system, such as a blister pack, the product cannot be imported under a SIP. Part 251 does not allow repackaging of drugs that breaches the container closure system, which would introduce unnecessary risk of adulteration, degradation and fraud for drugs imported under a SIP. Part 251 also does not permit affixing a conforming label to the outside of a drug product’s packaging in lieu of relabeling the immediate container of the product.
• Some drugs are excluded from being eligible drugs under Part 251 (e.g., biologics, controlled substances). Reference the definition of “eligible prescription drug” in 251.2 for more specifics regarding what is excluded.
• Explain how the SIP sponsor will address any concerns arising from the relabeling, storage and transport of each eligible prescription drug, including concerns related to controlling contamination, preserving sterility and ensuring stability for sterile drugs or drugs that require special storage conditions.
• At a minimum, include information from FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book) to show that each drug product is listed in the “active section.” This supporting information demonstrates that, for each HPFB-approved drug proposed for import, the FDA-approved counterpart is currently commercially marketed in the U.S.

Tips

• If a proposal provides only a high-level summary of statutory testing, FDA may presume the proposal described testing “to the extent possible” per section 251.3(e)(7). 
• Before importing, a SIP sponsor must file a pre-import request with detailed testing methods (unless the manufacturer conducts testing). This description must be sufficiently detailed for FDA to ensure compliance with section 251.16(d) requirements for statistically valid sampling, specifications testing and stability-indicating assays. 

Tips

• The acceptability of the qualifying laboratory could change. If a laboratory is inspected and receives an official action indicated (OAI) classification, or if the ISO 17025 accreditation for the laboratory expires, that laboratory would no longer meet qualifying laboratory requirements. FDA recommends the state develop a plan to assure the ongoing compliance of the laboratory and a contingency plan if the laboratory no longer meets requirements.
• A qualifying laboratory must be in the U.S. and approved by FDA as part of the SIP proposal review and authorization.

Tips

• Section 251.13(b)(4) specifies that, at the time the drug is sold or dispensed, the labeling of the drug must be the same as the FDA-approved labeling under the applicable NDA or ANDA, with certain exceptions.
• After a new version of the labeling for the FDA-approved counterpart is authorized by the FDA, prompt revision, submission to the agency and implementation of revised labeling are required to ensure the imported drugs under a SIP comply with section 505 of the FD&C Act. After the new version is approved by the FDA, promptly submit revised imported drug labeling that includes the new labeling changes. 
• It is the SIP sponsor’s responsibility to monitor for FDA-approved drug labeling changes (e.g., using Drugs@FDA). If the labeling is not available on Drugs@FDA, SIP sponsors can consider reviewing other labeling databases (e.g., FDALabel).
• SIP proposals that do not include all the package sizes available for the FDA-approved counterpart should only include package sizes proposed for importation from the “how supplied/storage and handling” section of the proposed prescribing information. 
• Repackaging or relabeling of eligible drugs must be accomplished in the U.S.
• Proofread for any unintentional edits or changes, especially for container and carton labeling.
• On the container label or carton labeling, include a space between the dose and unit (e.g., “28 mg,” not “28mg”). 
• Ensure the proposed container label and carton labeling are clear and legible.
• Submit all proposed labels and labeling. If a drug product has container and carton labeling, submit both. 
• The statement: “[This drug was/These drugs were] imported from Canada without the authorization of [name of applicant] under the [name of SIP sponsor] section 804 importation program” should be added to the prescribing information and immediate container label and outside package, but not to the patient labeling (medication guides, patient package inserts and/or instructions for use).
• Ensure the name of the applicant in the required statement, “[This drug was/These drugs were] imported from Canada without the authorization of [name of applicant] under the [name of SIP sponsor] section 804 importation program],” in all the proposed imported drug labeling is correct. If a SIP sponsor is unsure of the applicant’s name, refer to FDA’s Orange Book.
• Ensure the proposal includes a side-by-side comparison of the FDA-approved labeling and the proposed labeling, including the prescribing information, carton and container labeling and patient labeling, with all differences annotated and explained.
• Add the importer’s name and place of business at the end of the prescribing information in addition to the “how supplied/storage and handling” section. FDA also recommends adding the importer’s information at the end of the medication guides, patient package inserts and/or instructions for use.

In the event a SIP proposal is authorized, FDA may review labeling for the eligible prescription drugs intended for importation when it considers a pre-import request for those drugs. 

Tips

• Refer to our state importation program enhancements webpage for updates.
• It is useful to do the following so HHS can evaluate the cost savings analysis to see if it meets the requirements of Part 251:
  • Include a forecast of the per-unit prices for each product, and the total expenditures on these products in the aggregate, for each year under the proposal.
  • Include a baseline forecast covering the same scope of products and total expenditures the state would experience, absent the importation plan for each year.
  • Include the data source for each of the price estimates referenced in the proposal.
  • Ensure the data, sources and description of the analytic methods referenced in the proposal are such that a qualified person can reproduce the analysis.
  • Include a description of how HHS may access the data, if the proposal does not contain the underlying data.
  • When applicable, discuss the incidence of cost savings (e.g., how the cost savings are distributed among patients, the participating state, wholesale distributors, pharmacies, hospitals and third-party payers).
  • When applicable, discuss whether cost savings to the American consumer represent reductions in out-of-pocket spending, or in some other form of compensation (e.g., “cost savings that are passed onto consumers in other ways, such as increasing the number of people covered by a state program, or increasing the availability of drugs covered by the program.”).

Tips

• The SIP proposal should clearly distinguish between the responsibilities of the foreign seller and the importer and describe the systems and processes in place to fulfill applicable responsibilities. For instance:
  • Foreign seller: Assigns, affixes or imprints a section 804 serial identifier to each package and homogenous case intended for sale to the importer in the U.S. The section 804 serial identifier is a unique alphanumeric serial number of up to 20 characters. The section 804 serial identifier is a different identifier than the serial number that forms part of the product identifier required under section 582 of the FD&C Act.
  • Importer (or its authorized relabeler/repackager): Affixes or imprints the product identifier on each package and homogenous case of an eligible prescription drug in accordance with section 582 of the FD&C Act. A product identifier is a standardized graphic that includes the product’s NDC and a unique serial number (collectively, the standardized numerical identifier), lot number and expiration date (sections 581(14) and (20) of the FD&C Act). The product identifier must appear in human-readable form and as a machine-readable data carrier that conforms to standards developed by a widely recognized international standards development organization. For packages, this data carrier is a two-dimensional data matrix barcode. Visit Product Identifiers Under the Drug Supply Chain Security Act Questions and Answers for more information regarding the product identifier.

Tip

• Include adequate details regarding all FDA-required adverse event reporting and consumer inquiry response procedures. At a minimum, these should include assessment of seriousness, assessment of expectedness and reporting adverse drug event information to FDA and the manufacturer.

Tips

• Clearly describe the specific processes and communication channels for how recall or market withdrawal information will be obtained from manufacturers and shared among all parties (SIP sponsor, foreign seller, importer, FDA and manufacturer).
• The plan should establish clear contact information, escalation procedures and timeframes for notification among all parties in the supply chain.
• The plan should clearly delineate the specific responsibilities of each party (SIP sponsor, foreign seller, importer) in the recall communication chain.
• Create detailed plans that include specific procedural documents for the parties.

Tip

• Provide specific written compliance policies, procedures and protocols that were created as part of the SIP’s compliance plan.