Transcript 2010-FDASeminar-Part-II

Drug Imports & Exports
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Import/Export of Drugs
Chicago District-Import Team
August 26,2010
Michael Giammanco, CSO
Sherea L. Dillon, CSO
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Topics to Cover
• Drug Imports and Exports
• Errors Commonly Seen at O’Hare
• What is required for Review
– Affirmation of Compliance
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•
•
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Registration and Listing
NDA/ANDA/
Manufacture Name and Location
Reason for USRG
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Definition: “Drug” [201(g)(1)]
Article…
– Intended to diagnose, cure, mitigate, treat or
prevent disease in man or other animals
– Intended to affect the structure or any function
of the body of man or other animals (other than
food)
– Recognized in the USP/NF, HPUS or any
supplements
– Intended for use as a component of a drug 4
Drug Imports & Exports
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IMPORTED DRUG PRODUCT
• 80% APIs
• 40% finished drugs
• Heparin sodium adulteration
• DEG
• Melamine
• Drug Diversion (ketamine)
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Registration and Listing
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R & L Requirements
[510(j) & 21 CFR 207]
All foreign firms that manufacture, prepare,
propagate, compound, or process a drug
imported or offered for import into the U.S. are
required to…
1. Register their name and place of business
2. List all drug products imported or offered for
import into the U.S. (FDA form 2657)
3. Designate a U.S. Agent
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R & L Requirements
•
•
•
•
Manufacturers: APIs & finished drug products
Repackers and relabelers
Control laboratories: registration only
Domestic manufactures that pack/repack, label/relabeled, etc.
drugs under the Import for Export (IFE) requirements
• NDC #:
– FDA requests but not require that it appears on the product
label or labeling
– If NDC # appears on the label it must comply with regulation
[21 CFR 207.35 (b)(3)]
• Registration & Listing does not indicate FDA’s approval of a
firm or its products [21 CFR 207.39]
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R & L Requirements
–
Registration must be renewed annually
–
Registration required before any application is
approved
–
Listing information must be updated:
• Every June and December or
• Discretion of the registrant or
• When any change occurs
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R & L Requirements
U.S. Agent (21 CFR 207.40(c))
Each foreign drug establishment must designate only
one U.S. agent
Must be physically located in the U.S.
Point of contact between FDA and foreign firm on all
drug registration & listing matters and requirements
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R & L Requirements
U.S. Agent (21 CFR 207.40(c))
Letter of designation must:
Be prepared on the foreign firm's letterhead
Be signed by authorizing official of the firm
Contain the following:
- Name of the firm's designated U.S. Agent
- Address
- Telephone/fax numbers, and
- E-mail address
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R & L Requirements
• Listed products: assigned National Drug Code number
(NDC #)
• NDC # identifies the following:
– Manufacturer or distributor
– Drug
– Trade package size and type
• Un-listed products are misbranded [502(o)]
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Listing Exemptions
• Component of a drug (e.g. ingredients or non-API
intermediates used to synthesize APIs)
• Drugs not for importation into U.S. (i.e. FTZ)
• Drugs offered under Investigational New Drug (IND)
[21 CFR 312]
• Research for own study only and not for research in
humans (If distributed by someone and research is
conducted by someone else then, not exempt)
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R & L Information
FDA Forms: http://www.hhs.gov/forms
NDC Directory: www.fda.gov
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Drugs: Approved/ DESI/
Investigational/ OTC
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Importation
• Commercial Shipments
transmitted to Chicago
–
–
–
–
–
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Approved Drugs
Unapproved Drugs
Investigational New Drugs
Over the Counter OTC
DESI
Drugs for Research and
Development
– PLAIR (Pre-Launch Activities
Importation Requests)
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Prescription (Rx) drugs [503(b)(1)]
• These drugs cannot be used safely without
medical supervision
Examples:
• Injectable* drugs or
• drugs to treat serious conditions like heart
disease, cancer, or fertility problems
* Generally, injectable drugs are Rx, but insulin is not Rx in every
state.
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MR: IND vs. NDA vs. ANDA
NDA vs. ANDA: The differences in the two are noted in
Green. IND eventually becomes NDA
(Brand Name Drug)
NDA Requirements
1. Animal Studies*
2. Clinical Studies*
3. Bioavailability Studies
4. Chemistry
5. Manufacturing
6. Controls
7. Labeling
8. Testing
(Generic Drug)
ANDA Requirements
1-3. Bioequivalence
4. Chemistry
5. Manufacturing
6. Controls
7. Labeling
8. Testing
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Marketing requirements
(NDA/ANDA)
Approved new drug must be:
1. Manufactured, packaged, or labeled at a
facility covered in the application using
the formulation and process approved
2. Manufactured using an API supplied by a
manufacturer covered in the application
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Definition: Over-the-counter (OTC) drug
• All other drugs that can be used safely without
medical supervision
Examples:
• Medications for fever such as aspirin and
acetaminophen
• Preparations for the common cold or allergies
• Antacids, and
• Some first aid antibiotics
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Definition: Over-the-counter (OTC) drug
• Do some OTC products have NDA/ANDAs?
– Yes
– No
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OTC DRUGS
• Most OTC drugs on market not covered by
approved NDAs
• Large number of OTC drugs on market in
1972 did not have FDA approval
• Agency decided to have a class-by-class
review for OTC drugs instead of NDAs
• Final rules in effect 21 CFR 331-358
• Negative monographs found in 21 CFR
310
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OTC DRUGS
• Where there is a final monograph (FM), OTC
drug must meet the FM including labeling and
formulation
• Product must also comply with all other labeling
requirements of the FDCA
• Drug must be manufactured under cGMPs
• Firm is registered and the product is listed
• Some drugs switched from Rx to OTC still
require NDA (ibuprofen, Advil)
• Timed-release drugs require approval 21 CFR
310.502(a)(14)
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Chemical or Drug
• Per the FDCA, chemicals can be drugs,
but not all chemicals are drugs
– • Regulation 21 CFR 201.128, concerns the
meaning of “intended uses”– Intent is
determined by labeling, advertising matter,
oral or written statements
• GHB, GBL, DMSO, Procaine
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API Use in Clinical Studies
(a.k.a. IND) [21 CFR 201.122(b)]
• Must be covered by an active IND
• Must be going to person(s) authorized in the IND
• Drugs for clinical studies may not be used for
manufacturing.
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Marketing Requirements (MR): DESI
• Review initiated in response to the Drug Amendments
of 1962 to assess the effectiveness of drugs that had
been previously found to be safe under the Act
• DESI drugs are drugs that were the subject of pre1962 (safety only) NDAs and drugs that are identical,
related, and similar to such drugs [21 CFR 310.6]
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MR: DESI
• Once final order issued and any appeals exhausted,
application approval required for continued marketing
• Continued marketing permitted (exercise enforcement
discretion per CPG 7132C.02 (Sec. 440.100)) while
administrative process and any judicial appeals are
pending (DESI pending) and may be recognized as
part of the "DESI" drug
• CDER's policy: There are no such drugs as
"grandfathered drugs"
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Import for Export
Foreign Trade Zones
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MR: The 1996 Export Reform Act
Import for Export (IFE) [801(d)(3)]
• Allows importation of violative articles (including
finished drugs) intended for export [801(e) & 802] only
if further processed
• FDA must be provided with certain information:
– Written statement article is to be further processed,
id manufacture, processor, packer, distributor or
any entity that had possession of the article
– COA to identify the article
– Records when requested
• Must execute a bond for any liquidated damages
• Must maintain records of use and/or destruction
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• Must destroy any article not used in production
MR: The 1996 Export Reform Act
Import for Export (IFE) [801(d)(3)]
• Article can be refused admission if credible evidence
that it is not intended to be further processed
• Prohibited Acts [301(w)]: Exempts exportation
– False information and statement
– Introduction into interstate commerce any article
(including finished)
– Not submitting and maintaining records and COA
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MR: Foreign Trade Zone (FTZ)
• CBP’s designation to exempt from payment of duties, taxes and
bonds and considered by them to be outside U.S.
• Articles not offered for consumption, thus not considered
“imported or offered for import”
• If in FTZ, subject to FDA laws since considered within the
“territory” of the U.S.
• 801 does not apply until article is out of FTZ
• Introducing unapproved new drugs into FTZ violates new drugs
[355(a)] and prohibited [301(d)]
• Can bring into FTZ articles (bulk or finished) pending approval
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How we see your entry
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Affirmations of Compliance
Human Rx
Animal Rx
• NDA/ANDA
• DLS/NDC
• Registration
• NADA/ANADA
• DLS/NDC
• Registration
OTC
• DLS/NDC
• Registration
• NDA/ANDA*
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Affirmations of Compliance
PLAIR (Pre-Launch Activities Importation Request)
• CDER Approval
Investigational
• IND
Research Use
• Statement of Intended Use
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Common Errors Made on Drugs
• Submitting Affirmation of Compliance for Animal
and Human Drugs in the Affirmation Section
– Many Brokers put the NDA/ANDA in the product
description. This is incorrect. It should go in the
Affirmation of Compliance Section
• Multiple NDAs and uses should be filed on
different lines of the entry.
– Different NDAs should be on different lines, to avoid
errors, different purposes
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Common Errors Made on Drugs
• Drug Compounding information should be
submitted to FDA when entry is made and
should have the proper documents for release.
• Drugs not listed
• Imported Drug does not reflect Product code
• Quantity Description
– Bulk API vs. Finished Drug
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Drug Imports & Exports (cont)
• Importer given opportunity to bring product into
compliance.
• Products which are not brought into compliance
are refused admission into the U.S.
• Refused articles must either be destroyed or reexported
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Thank you!
QUESTIONS?
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