The U.S. Food and Drug Administration (FDA) has the authority to inspect any FDA-registered facility. Facilities located outside the U.S. that refuse an FDA inspection may be placed on Import Alert 99-32, “Detention Without Physical Examination of Products from Firms Refusing FDA Foreign Establishment Inspection”. All products exported to the U.S. by a facility on the Import Alert are subject to Detention Without Physical Examination (DWPE) until FDA is able to inspect the facility.
Import Alerts are public information that can damage a brand’s reputation. Delayed or refused shipments resulting from Import Alerts can also strain relationships with buyers. Thus, it is advised to accept an inspection without hesitation. FDA may issue a Notice of Inspection at any time, so you should prepare by ensuring your facility is compliant with FDA Current Good Manufacturing Practices (CGMPs) and other regulatory requirements.
Food Facility Inspections
FDA requires food facilities to respond to inspection requests within 24 hours. The Agency may interpret a lack of response as refusal of inspection. FDA communicates an inspection request with a facility’s U.S. Agent, so it’s prudent to designate a reliable Agent. When preparing for an inspection, you should familiarize yourself with common inspection violations so you can ensure you don’t make the same mistakes.
We invite you to utilize our webinar recording on how to handle an FDA food facility inspection to help you prepare. For customized preparation assistance, Registrar Corp can dispatch a Food Safety Specialist to your facility to conduct a Mock FDA Inspection. As part of this inspection service, our Specialist will help identify potential food safety problems in the structure, processes, procedures and documentation used in your daily production.
Drug Facility Inspections
There are a variety of actions that FDA may interpret as refusal of a drug facility inspection, including refusing an FDA inspector entrance into a facility, trying to postpone a scheduled inspection date without a reasonable explanation, and more. Registrar Corp’s article on FDA drug facility inspections will help you understand the different types of FDA inspections, how FDA investigators prepare for inspections, and what to expect during an inspection.
Our Facility Is Under Import Alert for Inspection Refusal. What Can We Do?
To seek removal from Import Alert 99-32, a facility must petition for inspection by FDA. FDA states that it may be at least a year before FDA can return to inspect a facility that initially refused. Given this, full cooperation with FDA inspection is imperative to avoid loss of profits from an avoidable Import Alert.
For more information about FDA inspections or Import Alerts, contact Registrar Corp by phone: +1-757-224-0177, email: [email protected], or chat with a Regulatory Advisor 24 hours a day at www.registrarcorp.com/livehelp.
On February 26, 2019, the U.S. Food and Drug Administration (FDA) published a proposed rule to establish final monograph regulations for over-the-counter (OTC) sunscreen drug products. If finalized, the rule will update conditions under which OTC sunscreen products may be marketed in the United States.
Since issuing an indefinite stay on a 1999 final monograph, FDA has mostly regulated Sunscreen products under enforcement discretion. In 2011, FDA clarified its enforcement approach to OTC sunscreen products through a draft guidance that was later finalized in 2018. At that point in time, FDA also issued a final rule for the labeling of OTC sunscreen drug products and established mandatory parameters for broad spectrum, sun protection factor (SPF) and water resistance testing. This final rule was codified in 21 CFR 201.327.
FDA’s new proposed rule would lift the stay on the 1999 final monograph as well as establish the following major provisions:
GRASE Status of Sunscreen Active Ingredients
The rule proposes that zinc oxide and titanium dioxide remain classified as generally recognized as safe and effective (GRASE) for use in sunscreens at concentrations of up to 25 percent.
Aminobenzoic acid and trolamine salicylate would be classified as not GRASE for use in sunscreen as FDA has determined the risks posed by these ingredients outweigh their benefits. Drug products containing non-GRASE ingredients are considered misbranded and prohibited from being marketed in the U.S.
Additionally, the rule proposes that the following twelve ingredients would be excluded from the final monograph because there is insufficient data to determine whether they are GRASE:
- Padimate O
Many of these ingredients are considered GRASE under the 1999 monograph, meaning sunscreen products with these ingredients can currently be marketed without a new drug application (NDA). If FDA’s new proposed rule becomes final, sunscreen products with these ingredients may not be introduced into interstate commerce one year after the final rule becomes effective. FDA has proposed an effective date for the final rule of November 26, 2019.
GRASE Statuses of Sunscreen Dosage Forms
The rule proposes to classify oils, lotions, creams, gels, butters, pastes, ointments, and sticks as GRASE dosage forms for sunscreens. Sprays would also be GRASE, contingent on testing to minimize risks from inhalation (particle size restrictions) and flammability (flammability and drying time testing).
Sunscreens in powder form would be eligible for inclusion in the final monograph pending additional scientific data supporting their safety. Powder sunscreens would also be subject to the same particle size restrictions as sprays. Other dosage forms, such as wipes, body washes, and shampoos would be considered new drugs, which require FDA approval of an NDA to market in the U.S.
Changes to Sunscreen Labeling
The rule proposes to require a sunscreen’s statement of identity to list the sunscreen active ingredients in alphabetical order followed by “Sunscreen” and the product’s dosage form (e.g. “Titanium Dioxide, Zinc Oxide Sunscreen Lotion”). The rule would also revise format requirements to make SPF, broad spectrum, and water resistance statements more prominent on a product’s principal display panel (PDP). Products that do not meet broad spectrum requirements must also include an asterisk next to the SPF value and an associated statement “*See Skin Cancer/Skin Aging Alert.”
Due to evidence showing “additional meaningful clinical benefit” from broad spectrum sunscreen products with an SPF of 60, the rule proposes to increase the maximum SPF displayed on sunscreen labels from 50+ to 60+. Sunscreen manufacturers would still be permitted to market products formulated up to 80 SPF as OTC.
Additionally, all sunscreen products over 15 SPF would be required to satisfy broad spectrum labeling and testing requirements. Among the other requirements of broad spectrum testing, the rule proposes that these products must meet a UVA I/UV ratio of 0.7 or higher.
Prohibition of Sunscreen-Insect Repellent Combinations
Given their use as pesticides, sunscreen-insect repellent combination products are also regulated by the Environmental Protection Agency (EPA). FDA has determined that these products cannot be labeled to “sufficiently ensure safe and effective use of the sunscreen component and provide adequate directions for use” due to incompatibility with EPA labeling requirements. The rule proposes to classify these products as not GRASE, which would effectively prohibit them from being marketed in the U.S.
What Industry Should Expect
FDA’s new proposed rule brings some significant possible changes for the sunscreen industry. As with any proposed rule, these provisions are not final; however, they illustrate FDA’s current thinking for the direction of sunscreen regulations. Sunscreen companies should familiarize themselves with the 1999 final monograph (21 CFR Part 352), required labeling based on effectiveness testing for OTC sunscreen drug products (21 CFR 201.327), and the newly proposed rule to prepare for compliance.
Registrar Corp assists sunscreen companies with FDA compliance. Our Regulatory Specialists can register your establishment and list your products with FDA, serve as your U.S. Agent, review your sunscreen’s labeling for compliance, and more. For more information, call us at +1-757-224-0177 or chat with a Regulatory Advisor 24/7 at www.registrarcorp.com/livehelp.
Beginning October 1, 2018, the U.S. Food and Drug Administration (FDA) will require electronic format for new Veterinary Master File (VMF) submissions, including amendments. FDA states that it will not accept paper VMF submissions after this deadline.
What Is A VMF?
FDA defines a VMF as “a submission that provides confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of veterinary drugs and drug substances.” A VMF holder can authorize third parties to reference the VMF’s material in support of submissions such as investigational new animal drug applications (INADAs) and abbreviated new animal drug applications (ANADAs) without disclosing trade secrets to industry.
What Are FDA’s Requirements For Electronic VMFs?
FDA does not require a specific format for electronic VMFs, but the FDA Center of Veterinary Medicine (CVM) does provide recommended guidelines for files in an electronic submission. After reaching out to FDA, the Agency has informed Registrar Corp that they will accept and encourage VMF submissions in Common Technical Document (CTD) format. Note that CTD is not the same as the Electronic Common Technical Document (eCTD) format required for most types of Drug Master Files (DMFs) and drug applications.
Beginning October 1, VMFs must be submitted through FDA’s Electronic Submissions Gateway (ESG) using the CVM version of the eSubmitter software. Electronic submissions to CVM require registration with both ESG and the CVM Electronic Submission System (ESS). These registrations may take several weeks as they involve multiple back-and-forth communications with FDA, including written letters and test submissions.
Alternatively, you can make a time-consuming process quick and easy by having an experienced FDA Regulatory Specialist, such as Registrar Corp, assist with your VMF submissions. Registrar Corp can convert your paper VMFs to electronic format and submit them to FDA on your behalf. For more information, call us at +1-757-224-0177 or chat with a Regulatory Advisor 24/7 at www.registrarcorp.com/livehelp.
U.S. FDA Deadline Approaching for Prescription Drug Labels: New Product Identifier Requirements
Under the Drug Supply Chain Security Act (DSCSA), manufacturers, packagers, and repackagers of human prescription drugs must affix or imprint a “product identifier” to each package and homogenous case of product intended to be introduced in a transaction into US commerce. This process is known as “serialization.”
Manufacturers, packagers and repackagers of human prescription drugs must comply with this new requirement by November 27, 2018. After this date, the U.S. Food and Drug Administration (FDA) will consider drug products that do not bear a product identifier to be misbranded and in violation of FDA regulations.
Furthermore, industry will not be permitted to buy or sell prescription drug products that are not encoded with a product identifier after the following dates:
- November 27, 2018 for repackagers
- November 27, 2019 for wholesale distributors
- November 27, 2020 for dispensers
Formatting a Product Identifier
A product identifier should include the product’s National Drug Code (NDC), unique serial number, lot number and expiration date in human and machine-readable formats.
The machine-readable format should be a 2D data matrix barcode when affixed to or imprinted on a package (the smallest individual saleable unit of product for distribution by a manufacturer or repackager that is intended by the manufacturer for ultimate sale to the dispenser of such product) or a linear or 2D data matrix barcode when affixed to or imprinted onto a homogenous case of product (a sealed case containing only product that has a single NDC number belonging to a single lot).
Implications for Drug Listings
As of last year, FDA requires that drug establishments “certify” listings that have not been changed since the previous calendar year during the annual registration renewal period. In an email to industry this week, FDA stated that manufacturers and repackagers that have not yet incorporated the new product identifier requirements into their labels should not certify that their drug listings are up-to-date during the upcoming registration renewal period (October 1, 2018 to December 31, 2018). Industry should submit a new sampling of the labeling incorporating the product identifier as an update to their listing.
Registrar Corp can provide guidance on FDA’s new product identifier requirements and update drug listings on your behalf. For more information, complete the form below. You can also reach us by phone at +1-757-224-0177 or chat with a Regulatory Advisor 24 hours a day at www.registrarcorp.com/livehelp.
The U.S. Food and Drug Administration (FDA) recently published the Fiscal Year (FY) 2019 fee schedules for the Generic Drug User Fee Amendments (GDUFA) and Medical Device User Fee Amendments (MDUFA). FY 2019 rates for both amendments take effect on October 1, 2018. To keep industry updated on these requirements, Registrar Corp outlines upcoming changes to these fees below.
Fees for Drug Facilities
GDUFA requires user fees from certain types of drug facilities. On October 1, 2018, generic drug facilities are required to pay any applicable facility fees to FDA. Additionally, GDUFA requires fees for new Type II Drug Master File (DMF) and Abbreviated New Drug Application (ANDA) submissions to FDA. You will find a table of these fees below.
Notable Changes to GDUFA in FY 2019
- ANDA Program Fees – In FY 2018, FDA introduced program fees for ANDA holders. These facilities pay a user fee based on the number of approved ANDAs they hold on October 1 of a given year. The FY 2019 ANDA program fees reflect an approximate 17% increase from the previous year.
- Type II DMF Submission Fees – In FY 2018, the fee for a single Type II DMF submission to FDA was $47,829. FY 2019 will see an approximate 15% increase to $55,013.
You can view a comparison between the FY 2018 and FY 2019 GDUFA fees below:
FY 2019 GDUFA Fees
|Active Pharmaceutical Ingredient (API)
|Finished Dosage Form (FDF)
|Contract Manufacturing Organization (CMO)
|ANDA Program Fees – Based upon the number of approved ANDAs held
|Large (20 or more ANDAs)
|Medium (6 – 19 ANDAs)
|Small (5 or fewer ANDAs)
|Type II DMF
Fees for Medical Device Establishments
MDUFA requires all FDA-registered establishments to pay a user fee during their annual registration renewal. The FY 2019 establishment registration fee for all establishments is $4,884. According to the publication of MDUFA fees, FDA does not recognize an establishment as legally registered until this fee is paid.
Additionally, MDUFA requires fees for the submission of certain medical device applications to FDA. Small businesses, defined by MDUFA as having gross sales or receipts of no more than $100 million during the most recent tax year, may qualify for discounts to application fees. All medical device application fees reflect an approximate 3-4% increase from the previous year.
You can view a comparison between the FY 2018 and FY 2019 MDUFA fees below:
FY 2019 MDUFA Fees
|Annual Establishment Registration
|De Novo Classification
|PMA, PDP, PMR, BLA
|BLA efficacy supplement
|PMA annual report
Not sure which fees you may be subject to? Registrar Corp’s Regulatory Specialists can help determine your applicable fees and facilitate payment with FDA. Call us at +1-757-224-0177, or chat with a Regulatory Advisor 24 hours a day at www.registrarcorp.com/livehelp.
*Update: In January 2019, FDA extended the eCTD compliance date for Type III DMFs an additional 12 months (May 5, 2020).
On April 25, 2018, the U.S. Food and Drug Administration (FDA) extended the deadline for the mandatory use of electronic common technical document (eCTD) format for type III Drug Master File (DMF) submissions by one year. eCTD format will now be required for type III DMF submissions beginning May 5, 2019.
Type II, type IV, and type V DMF submissions to FDA must be in eCTD format beginning May 5, 2018. Additionally, FDA recommends using eCTD format to file Type III DMF submissions despite the extension. eCTD submissions must be filed through FDA’s Electronic Submissions Gateway (ESG). The process to obtain access to ESG can take several weeks, so it is prudent for businesses to begin working toward compliance as soon as possible.
You can make compliance easy by having Registrar Corp manage your DMF submissions. Our Regulatory Specialists use FDA’s ESG to submit new DMFs to FDA in eCTD format as well as convert existing DMFs to eCTD to make future updates, reports, and amendments easier. If you are not certain if your DMFs qualify for the extension, Registrar Corp can verify your classifications at no cost.
For more information, contact us by phone at +1-757-224-0177 or chat with a Regulatory Advisor 24 hours a day: www.registrarcorp.com/livehelp.
*Update: In January 2019, FDA extended the eCTD compliance date for Type III DMFs to May 5, 2020.
Beginning May 5, 2018, the U.S. Food and Drug Administration (FDA) will require electronic common technical document (eCTD) format for all new Drug Master File (DMF) submissions, including reports and amendments. FDA states that it will reject DMF submissions not in eCTD format following this deadline.
What is eCTD?
eCTD is currently FDA’s standard submission format for new drug applications (NDAs), investigational new drug applications (INDs), abbreviated new drug applications (ANDAs), and certain biologics license applications (BLAs). FDA states that DMFs are typically submissions to these applications and, as such, are subject to electronic submission required by section 745A(a) of the Federal Food, Drug, and Cosmetic (FD&C) Act.
After the deadline, FDA will require users to submit DMFs in the eCTD version supported by the FDA Data Standards Catalog. Additionally, an April 2017 FDA guidance document establishes technical specifications for aspects such as submission structure, file formats and versions of submission components, and required locations for datasets and study information.
Existing DMFs that are not in eCTD format, including those in paper form, do not require resubmission; however, additional submissions such as annual reports, supplements, and amendments to these DMFs must be submitted through ESG in eCTD. Existing paper DMFs voluntarily converted to eCTD will retain their current DMF number. Companies typically convert their existing paper DMFs to eCTD to expedite the review process of a NDA or ANDA that references the DMF.
How Do I Send an eCTD Submission?
eCTD submissions 10GB or smaller must be sent through FDA’s Electronic Submissions Gateway (ESG). Prior to accessing ESG, a user must request an application number from FDA, register for an ESG account, and configure their computer to communicate with the gateway. FDA advises users to perform a series of tests prior to submission. The process for ESG access may require several weeks.
Alternatively, you can make the process quick and easy by having a Regulatory Specialist, such as Registrar Corp, convert your DMF submissions to eCTD format and submit them to FDA through ESG. For more information, contact us by phone at +1-757-224-0177 or chat with a Regulatory Advisor 24 hours a day: www.registrarcorp.com/livehelp.
On January 2, 2018, the U.S. Food and Drug Administration (FDA) removed all drug establishments that did not renew their FDA registrations for 2018 from its active registration database. The Agency also removed all uncertified drug product listings from publication.
- FDA removed 1,256 of the 10,496 drug establishments in FDA’s database as of December 31, 2017 (12%)
- FDA removed 30,786 of the 118,255 drugs listed in FDA’s database as of December 31, 2017 (26%)
Companies that would like to verify that their drug establishment registrations or drug product listings are active with FDA can do so at no cost using the following links:
Annual FDA Drug Establishment Registration
FDA requires registered drug establishments to renew their registrations between October 1 and December 31 each year. Those that fail to renew by the deadline are removed from FDA’s database, and drugs manufactured in unregistered facilities are considered misbranded. Marketing misbranded drugs in the USA is a prohibited act that may be met with seizure and injunction.
Registrar Corp can verify whether your registration was properly renewed at no cost. Verify your registration now.
New “Blanket No Change Certification” Requirements for Drug Product Listings
FDA requires drug establishments to report any changes to product listings in June and December each year. Until recently, unchanged listings required no action. FDA introduced a change for the 2017 renewal period requiring registered drug establishments to submit a “blanket no change certification” in structured product labeling (SPL) format for all drug listings that required no updates within the year. Unchanged listings that were not properly certified during the 2017 renewal period were removed from publication, making it a prohibited act for those products to be marketed in the USA.
Registrar Corp can verify whether your listings are currently on file with FDA at no cost. Verify your listings now.
Registrar Corp is a U.S. FDA consulting firm that helps drug establishments comply with FDA regulations. Registrar Corp assists with FDA registration, drug product listings, drug labeling, drug master files (DMFs), and more. For questions or assistance, visit www.registrarcorp.com, call +1-757-224-0177, or chat with a Regulatory Advisor 24-hours a day at www.registrarcorp.com/livehelp.
This article was originally published as a press release.
The medical device and drug industries saw numerous regulatory developments in 2017. The U.S. Food and Drug Administration (FDA) introduced new requirements, fees, deadline extensions, and exemptions. Below, Registrar Corp provides an overview of regulatory highlights this year.
FDA Removed Medical Device and Drug Establishments that Did Not Register for 2017
Medical device and drug establishments that failed to properly renew their registrations for 2017 were removed from FDA’s active registration database. The Agency will likely do the same in 2018. Marketing medical devices and drugs without a valid registration is a prohibited act that may be met with seizure and injunction.
FDA Extended the UDI Compliance Date for Class I Devices to 2020
FDA issued a letter in June announcing its intention to extend the universal device identifier (UDI) compliance dates for class I and unclassified devices. The letter proposes to push the UDI labeling compliance date for these devices to September 24, 2020.
FDA Exempted Certain Class II Devices from 510k
In July, FDA exempted certain class II medical devices from premarket notification (510k) requirements. The exempt devices “are sufficiently well understood and do not present risks that require premarket notification review to provide a reasonable assurance of safety and effectiveness.” View a list of the exempt devices here.
The Compliance Date Passed for the Consumer Antiseptic Wash Final Rule
As of September, over-the-counter (OTC) consumer antiseptic washes containing any of nineteen certain ingredients are not permitted to enter interstate commerce without approval of a new drug application (NDA). FDA made this determination after discovering there was insufficient evidence to support the ingredients’ safety and effectiveness for their intended use.
FDA Published FY 2018 User Fees for Medical Devices and Generic Drugs
The Medical Device User Fee Amendments (MDUFA) and Generic Drug User Fee Amendments (GDUFA) were reauthorized for fiscal year (FY) 2018. The amendments introduced differences in rates from FY 2017, as well as new types of fees for certain facilities and submissions.
View the list of fees for medical device establishments here.
View the list of fees for drug establishments here.
FDA Introduced a New Verification Requirement for U.S. Agents of Medical Device Establishments
The U.S. Agent of medical device establishments located outside of the United States is now required to confirm this role with FDA. Agents must accept their designation through the FDA Unified Registration and Listing System (FURLS). If the Agent does not respond to a verification email within ten days, the establishment will need to designate a new Agent.
FDA Introduced Annual Certification Requirement for Unchanged Drug Listings
The 2017 registration renewal period introduced a requirement for drug establishments to submit a “blanket no-change” certification for drug listings that did not receive any changes to data or labeling during the year. Certifications must be submitted in structured product labeling (SPL) format.
FDA Published Final Guidance for UDI Direct Marking Requirements
In November, FDA issued a final guidance to clarify a device labeler’s responsibilities for UDI direct marking requirements. Class II devices must comply with direct marking requirements by September 24, 2018. During a December webinar, FDA stated that they do not intend to enforce these requirements for class I and unclassified devices until September 24, 2022.
FDA Issued a Final Rule on the Safety and Effectiveness of Triclosan in Health Care Antiseptics
FDA finalized a rule prohibiting the use of Triclosan and 23 other active ingredients in OTC antiseptics for health care environments. After December 20, 2018, health care antiseptics containing these ingredients will not be permitted to enter interstate commerce without FDA approval of an NDA.
As we cross into 2018, Registrar Corp will continue to keep the medical device and drug industries informed about important FDA regulations. For assistance with FDA requirements in either industry, call us at +1-757-224-0177, or chat with a Regulatory Advisor 24/7 at www.registrarcorp.com/livehelp.
On December 20, 2017, The U.S. Food and Drug Administration (FDA) published a final rule that will prohibit the inclusion of commonly used ingredient triclosan and 23 other active ingredients in antiseptics for health care environments. Following the rule’s compliance deadline of December 20, 2018, health care antiseptics containing any of the covered ingredients will not be permitted to enter interstate commerce without FDA approval of a new drug application (NDA). You will find a list of the covered ingredients below.
The scope of this rule only applies to antiseptic products (i.e. washes, scrubs, rubs, and skin preparations) used by health care professionals in health care settings. Antiseptic products intended for use by consumers are covered by two separate rules, one of which had a compliance deadline in September 2017.
Why are these ingredients prohibited?
The covered ingredients were initially part of a 1994 tentative final monograph for OTC antiseptic drug products. A 2015 proposed rule called for additional data to support the safety and effectiveness of these ingredients for use in health care antiseptic products. FDA did not receive any additional data, and the available scientific evidence surrounding the ingredients was insufficient to support a determination that they are generally recognized as safe and effective (GRASE).
FDA is delaying final rulemaking for at least one year on benzalkonium chloride, benzethonium chloride, chloroxylenol, alcohol (also known as ethanol or ethyl alcohol), isopropyl alcohol, and povidone-iodine. The Agency has stated that a determination for these ingredients will be dependent upon whether ongoing studies are eventually completed, and if so, when they are completed.
Not sure how this rule applies to your health care antiseptics? Registrar Corp’s Regulatory Specialists can conduct a full review of your antiseptic product’s ingredients and labeling. We review your product’s active ingredients to ensure that they conform to the requirements specified in the applicable FDA monographs for antimicrobial drug products. We also inspect your labeling to ensure that its content and formatting conform to numerous FDA drug regulations. In addition to an extensive report of suggested revisions, you will receive a print-ready label incorporating these changes. For assistance, call us at +1-757-224-0177 or chat with a Regulatory Advisor 24/7 at www.registrarcorp.com/livehelp.
Ingredients Deemed Not Generally Recognized as Safe and Effective under the Health Care Antiseptic Final Rule:
Iodophors (Iodine-containing ingredients)
• Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate)
• Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol)
• Iodine tincture USP
• Iodine topical solution USP
• Nonylphenoxypoly (ethyleneoxy) ethanoliodine
• Poloxamer—iodine complex
• Undecoylium chloride iodine complex
Combination of calomel, oxyquinoline benzoate, triethanolamine, and phenol derivative
Combination of mercufenol chloride and secondary amyltricresols in 50 percent alcohol