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.
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 April 2018, FDA extended the eCTD compliance date for Type III DMFs to May 5, 2019.
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
Once small and specialized, homeopathic drugs now comprise a nearly $3 billion industry. Following an increase in reported health concerns stemming from these products and a flurry of unsubstantiated health claims surrounding the industry, the U.S. Food and Drug Administration (FDA) is taking new measures to curb the widespread distribution of potentially harmful drugs labeled as homeopathic.
What are Homeopathic Drugs?
Homeopathy is a form of alternative medicine based on the principle of remedying health conditions using diluted solutions of substances that produce similar symptoms in a healthy patient.
The Food, Drug, and Cosmetic (FD&C) Act defines articles recognized in the official Homeopathic Pharmacopoeia of the United States as drugs. FDA states that homeopathic drugs “are subject to the same requirements related to approval, adulteration and misbranding as any other drug product.”
Despite this, the uniqueness of homeopathic drugs delayed them from the 1972 over-the-counter (OTC) drug review, which determined the safety and effectiveness of most OTC drugs on the U.S. market. Even now, FDA has not conducted a formal review of homeopathic drugs. Since 1988, a FDA Compliance Policy Guide (CPG) establishes provisions under which these products may be marketed without the prior FDA approval required of other drug products.
Why is FDA Cracking Down on Homeopathic Drugs?
Numerous homeopathic drugs contain potentially harmful ingredients. As recently as September 2017, a homeopathic drug facility received a Warning Letter, citing failure to establish adequate in-process controls for products containing multiple potentially toxic ingredients. One such ingredient was Nux vomica, a plant bearing constituents commonly used for rat poison.
Throughout 2017, FDA issued at least four additional letters to homeopathic drug manufacturers who failed to adequately test and control potentially toxic substances in their products. FDA charged the drugs in question as adulterated.
New Enforcement Approaches to Homeopathic Drugs
In addition to FDA, the U.S. Federal Trade Commission (FTC) has issued measures to mitigate the prevalence of unsubstantiated health claims made by homeopathic drug manufacturers. A 2016 FTC Enforcement Policy Statement requires homeopathic drug labeling to communicate that “there is no scientific evidence that the product works.” The label must also indicate that “the product’s claims are based only on theories of homeopathy from the 1700s that are not accepted by most modern medical experts.”
A December 2017 FDA draft guidance explains that the Agency intends to prioritize enforcement on products that are known to cause harm to patients, including those with reported health issues and those deemed adulterated under section 501 of the FD&C Act.
FDA states it will also focus increased attention on homeopathic drugs with less overt health concerns. According to the guidance, unapproved drugs intended to treat serious or life-threatening conditions may cause a patient to delay or discontinue treatment already generally recognized as safe and effective (GRASE). Homeopathic drugs designed for vulnerable populations (e.g. infants and the elderly) may pose significant health risks even in small concentrations, in spite of treatments that have already been determined GRASE. For this reason, these drug categories may see increased regulatory enforcement.
In the previously referenced Warning Letters, FDA maintains that “nothing in the FD&C Act exempts homeopathic drugs from any of the requirements related to adulteration, labeling, misbranding, or approval.” The letters and newly issued guidance suggest that FDA intends to expand efforts to hold homeopathic drug manufacturers accountable to the regulations derived from the FD&C Act.
Registrar Corp is a consulting firm that assists drug companies with U.S. FDA regulations. Our Regulatory Specialists can assist with FDA registration and drug listing, labeling requirements, and other drug regulations. For assistance or questions call +1-757-224-0177 or chat with a Regulatory Advisor 24 hours a day at www.registrarcorp.com/livehelp.
Drug establishments registered with the U.S. Food and Drug Administration (FDA) are required to renew their registrations with every year between October 1 and December 31. The 2017 renewal period marks the first time that registered establishments must submit a “blanket no change certification” for all drug product listings that required no updates within the year.
FDA requires drug establishments to report any changes to product listings in June and December each year. Until recently, unchanged listings required no action. This year, registrants must certify that all product listings which were not updated have had no changes occur to the data or labeling. Product listings that are neither updated within the year nor certified during the renewal period may be considered expired by FDA and removed from the Agency’s database. Marketing unlisted drugs in the United States is a prohibited act.
How can I obtain “blanket no change certification” for my drug product listings?
Registered drug establishments should submit a “Blanket No Change Notification” for all products that have not been updated during the current year to certify there were no changes to the data or labeling as part of their annual registration renewal. The notification must be submitted in structured product labeling (SPL) format. Structuring data in SPL format requires SPL authoring software. The SPL files can be submitted to FDA via the Agency’s Electronic Submission Gateway (ESG). Users may also use CDERDirect to submit for human drug listings. According to FDA, all SPL listing submissions will undergo a rigorous set of validation rules.
Registrar Corp can renew your FDA registration and certify or update your drug product listings using the required SPL format on your behalf. Our Regulatory Specialists are experienced in navigating FDA’s ESG and can complete your renewal quickly and properly. Contact us at +1-757-224-0177 or chat with a Regulatory Advisor online 24-hours a day at www.registrarcorp.com/livehelp.