When Is FDA Form 0356H Required? (w/Examples) + FAQs

Yes, FDA Form 0356h is required for all original New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), and Biologics License Applications (BLAs), as well as specific supplements including Prior Approval, CMC, Efficacy, and REMS submissions. 21 CFR 314.50(a) mandates this form as the official application cover sheet, creating an immediate barrier: incomplete or incorrect Form 0356h submissions trigger Refuse-to-File (RTF) or Refuse-to-Receive (RTR) actions, which delay drug approval timelines by 6 to 18 months and force complete resubmission of applications.

The consequence is severe. A 2021 study examining RTF letters found that FDA refuses applications for substantive reasons tied to quality, safety, and efficacy—with Form 0356h deficiencies representing the administrative gateway that prevents review from ever beginning. When this form contains missing facility information, incorrect establishment numbers, or mismatched data between Module 3 and the 0356h, the application sits in administrative limbo. Patients wait longer for therapies. Sponsors hemorrhage capital during extended review cycles.

Recent FDA data shows that incomplete Form 0356h submissions account for approximately 23% of all ANDA filing deficiencies during the initial 60-day filing review period.

What You Will Learn:

📋 Exact submission types requiring Form 0356h — Distinguish between mandatory versus optional scenarios across NDAs, ANDAs, BLAs, supplements, and amendments

🔍 Line-by-line field requirements — Master every section from applicant information to establishment data with real-world examples showing correct versus deficient entries

⚠️ Common mistakes causing RTF/RTR actions — Identify the top 10 discrepancies FDA reviewers flag, including FEI/DUNS errors, pending facility status mistakes, and missing API facilities

📊 Supplement categorization rules — Understand when Prior Approval, CBE-30, Changes Being Effected, Annual Reports, and REMS supplements need complete versus shortened forms

🎯 Strategic submission guidance — Apply best practices for facility listings, combination products, user fee cover sheets, and cross-referencing to Module 3 documentation

Understanding FDA Form 0356h: The Application Gateway

FDA Form 0356h serves as the official cover sheet for human drug and biologic applications. The form title reads “Application to Market a New or Abbreviated New Drug or Biologic for Human Use.” This document does more than introduce your submission—it provides FDA reviewers with critical metadata needed for proper routing, review assignment, user fee assessment, and facility inspection scheduling.

Form 0356h fulfills the regulatory requirement established under 21 CFR 314.50(a) for NDAs, 21 CFR 314.94(a)(1) for ANDAs, and 21 CFR 601.2(a) for BLAs. Without this completed form, FDA cannot legally accept your application for filing review. The form acts as a contractual declaration where you certify compliance with applicable laws and agree to submit safety updates as requested.

The current version of Form 0356h was released in July 2023 with an expiration date of March 31, 2026. FDA expects applicants to use this most recent version for all submissions. Using an obsolete version creates an immediate deficiency that triggers information requests during the filing review period.

Why This Form Exists

The FDA processes thousands of drug applications annually across three major centers: the Center for Drug Evaluation and Research (CDER), the Center for Biologics Evaluation and Research (CBER), and in some cases, the Center for Devices and Radiological Health (CDRH) for combination products. Form 0356h standardizes the information that FDA document room staff need to route submissions correctly, assign application numbers, calculate user fees, and prepare the application for scientific review.

Before this standardized form existed, applicants submitted varying cover letter formats that omitted critical facility information or buried key details in narrative text. Reviewers spent valuable time extracting basic information instead of evaluating scientific data. Form 0356h solved this problem by creating structured data fields that computer systems can process automatically.

The Refuse-to-File Consequence

During the first 60 days after FDA receives your submission, reviewers conduct a filing review to determine if your application is sufficiently complete for substantive scientific review. FDA MAPPs document 5200.7 establishes that incomplete or missing Form 0356h constitutes grounds for an RTF action under 21 CFR 314.101(d)(3).

An RTF action means FDA refuses to file your application for review. Your PDUFA date disappears. The review clock never starts. You must correct all deficiencies and resubmit the application as a complete new submission, paying user fees again if applicable. The typical delay ranges from 6 to 18 months depending on the complexity of deficiencies and time needed to gather corrected information.

FDA guidance on RTF actions emphasizes that reviewers communicate potentially easily correctable deficiencies to sponsors during the filing period, but Form 0356h errors often appear alongside other substantive problems, making correction impossible within the 60-day window.

When Form 0356h Is Absolutely Required

The requirement for Form 0356h depends on three factors: the type of submission, the regulatory pathway, and the nature of changes proposed. Understanding these triggers prevents costly submission mistakes.

Original Applications: Always Mandatory

Every original NDA, ANDA, and BLA must include a completed Form 0356h. This requirement appears in 21 CFR 314.50 for NDAs, 21 CFR 314.94 for ANDAs, and 21 CFR 601.2 for BLAs. No exceptions exist for this category.

Original NDA: A pharmaceutical manufacturer develops a new molecular entity for treating hypertension. The company conducts Phase 1, 2, and 3 clinical trials establishing safety and efficacy. When submitting the NDA under Section 505(b)(1), the application package must begin with Form 0356h in the first volume immediately after the user fee cover sheet (Form FDA 3397).

Original ANDA: A generic drug manufacturer seeks approval for a generic version of an approved brand-name statin. The ANDA relies on FDA’s previous finding of safety and effectiveness for the reference listed drug. Form 0356h appears in the first volume with the GDUFA user fee cover sheet (Form FDA 3794).

Original BLA: A biotech company develops a monoclonal antibody for cancer treatment. The BLA submission to CBER includes Form 0356h specifying applicant information, product description, clinical study details, and manufacturing facility locations. This form serves as the official request for permission to introduce the biologic product into interstate commerce under 21 CFR 601.2.

Efficacy Supplements: Required for Label-Changing Clinical Data

Efficacy supplements propose changes to approved products from among specific categories defined in 21 CFR 314.70 and 21 CFR 601.12. These supplements require complete Form 0356h with full establishment information.

Efficacy supplement triggers include:

• New or modified indication for use
• New or revised dose or dosing regimen
• New route of administration
• Comparative efficacy claim naming another product
• Significant alteration in patient population
• Switch from prescription to over-the-counter status
• Traditional approval of accelerated approval products
• Labeling or manufacturing changes requiring clinical data for approval

Real-World Example: An approved antidepressant currently indicated for major depressive disorder in adults seeks a new pediatric indication for adolescents aged 12 to 17. The sponsor conducted two adequate and well-controlled trials in the pediatric population. This efficacy supplement requires Form 0356h because it proposes a new indication requiring clinical data review.

The form must identify the supplement number in Field 8, select “Efficacy Supplement” in Field 21, and include complete establishment information in Field 28 for all facilities involved in manufacturing drug substance and drug product—even if facilities were previously approved. This redundancy allows FDA to verify no facility changes occurred since the last approval and ensures the manufacturing infrastructure supports the expanded indication.

CMC Supplements: Required for Chemistry Manufacturing Controls Changes

CMC supplements address chemistry, manufacturing, and controls modifications. These supplements require Form 0356h when submitted as Prior Approval (PA) supplements. The form ensures FDA can track facility additions, process changes, and specification modifications.

CMC triggers requiring complete Form 0356h include:

• Adding new manufacturing facilities for drug substance or drug product
• Changing the manufacturing site for sterile drug products
• Relaxing drug substance or drug product specifications
• Changing from one container closure system to another
• Major changes in synthesis or manufacturing process

Manufacturing Site Change Example: An injectable oncology drug approved with manufacturing at a facility in Ireland now adds a second manufacturing facility in Singapore. The sponsor submits a Prior Approval CMC supplement with Form 0356h listing both the existing Ireland facility (marked as active) and the new Singapore facility (marked as pending). Field 28 requires complete information for both sites including FEI numbers, DUNS numbers, manufacturing steps performed, and inspection readiness dates.

Failure to properly mark the Singapore facility as “new to this application” in the establishment section creates confusion during FDA’s pre-approval inspection scheduling. If FDA inspects the wrong facility or delays inspection due to unclear information, approval delays by months.

REMS Supplements: Mandatory for Risk Evaluation and Mitigation Strategies

When FDA requires a Risk Evaluation and Mitigation Strategy for your product, any modification to that REMS requires submission with Form 0356h. Section 505-1 of the FD&C Act governs REMS requirements, and modifications fall into major and minor categories.

Major REMS modifications require Prior Approval supplements with complete Form 0356h. These include:

• Adding or modifying elements to assure safe use (ETASU)
• Changing restricted distribution requirements
• Modifying patient monitoring or provider certification requirements
• Significant changes to Medication Guides required by the REMS

Example: An approved opioid medication has a REMS requiring prescriber certification and patient enrollment. The sponsor proposes adding a requirement for pharmacist counseling before dispensing. This major REMS modification requires a Prior Approval supplement with Form 0356h. Field 21 identifies “REMS Supplement” and the form includes any manufacturing changes needed to support new packaging or labeling associated with the modified REMS.

Minor REMS modifications require CBE-30 supplements that still include Form 0356h, though with potentially reduced establishment information if no facility changes occur. Examples include adding another drug to an existing single shared system REMS or updating contact information in REMS materials.

Resubmissions: Complete Form Required

When FDA issues a Complete Response letter identifying deficiencies that prevent approval, your resubmission addressing those deficiencies requires a new complete Form 0356h. The resubmission represents a new review cycle with a new PDUFA date, so FDA needs updated information about your application status.

Complete Response Resubmission: FDA issues a Complete Response letter for an NDA citing inadequate stability data and requesting additional clinical pharmacology information. Six months later, the sponsor completes the requested studies and submits the resubmission. This resubmission includes a new Form 0356h with Field 22 marked “Resubmission” and Field 27 explaining what deficiencies were addressed. All facility information must be current as of the resubmission date, reflecting any changes in facility status since the original submission.

If the Ireland manufacturing facility was marked “pending” in the original application but received approval during the interim period, the resubmission Form 0356h must mark it “active.” Leaving it as “pending” creates a discrepancy that triggers information requests.

When Form 0356h Is NOT Required

Understanding exemptions prevents unnecessary work and helps allocate resources efficiently. Several submission categories either omit Form 0356h entirely or use abbreviated versions.

Amendments to Pending Applications

Amendments provide additional information to FDA during review of a pending original application or supplement. Amendments to pending applications do not require new Form 0356h submissions. Instead, amendments include a cover letter identifying the application number, submission type being amended, and nature of information being provided.

Example: FDA issues an information request during review of a pending ANDA asking for additional stability data on the 24-month time point. The sponsor submits an amendment with a cover letter stating “Amendment to ANDA 123456 dated January 15, 2026, providing requested stability data through 24 months.” No Form 0356h accompanies this amendment because it supplements an already-filed application rather than initiating a new review cycle.

The key distinction: amendments augment existing submissions that FDA already accepted for filing. The original Form 0356h filed with the application provides the metadata FDA needs.

Annual Reports: Special Requirements

Annual reports update FDA on approved products and report certain changes that do not require prior approval. Annual reports for NDAs under 21 CFR 314.81(b)(2) and for BLAs under 21 CFR 601.12(d) have special Form 0356h requirements.

Annual reports may include a simplified Form 0356h focusing on changes being reported, but the full establishment section is not required unless new facilities are being added to the application. If the annual report only discusses distribution data, stability updates, and field alert reports with no facility changes, many sponsors omit Form 0356h entirely and rely on the cover letter to identify the submission.

Example: A sponsor submits an annual report for an approved NDA containing distribution information, stability commitment updates, and three field alert reports for complaints about packaging defects. No manufacturing changes occurred during the reporting period. The sponsor includes a cover letter identifying the NDA number and report period but omits Form 0356h because no changes requiring tracking occurred.

Contrast this with an annual report adding a new packaging facility in Brazil. This annual report requires Form 0356h with the establishment section completed to introduce the new facility to FDA’s tracking system.

Changes Being Effected (CBE) and CBE-30 Supplements

CBE supplements implement certain moderate changes that do not require prior approval but must be reported to FDA. The requirements for Form 0356h with CBE submissions depend on what changes are being made.

CBE supplements without facility changes: A sponsor submits a CBE supplement updating the product’s prescribing information to add a new phone number for medical information inquiries. This administrative labeling change requires a cover letter but may omit Form 0356h if guidance specific to the submission type allows it. However, including a simplified Form 0356h identifying the change type is considered best practice to ensure proper routing.

CBE-30 supplements with facility changes: A sponsor submits a CBE-30 supplement for a moderate formulation change that requires listing a new excipient supplier. This supplement requires Form 0356h with complete establishment information for the new supplier if that supplier performs testing that impacts the control strategy.

The deciding factor is whether FDA needs to track facility information for compliance and inspection purposes. If yes, Form 0356h is mandatory.

Manufacturing Changes Reports and Other Specified Categories

Some post-approval submissions follow alternative reporting mechanisms that replace traditional supplement submissions. These include:

Manufacturing Changes Reports: For certain biotechnology products, changes may be reported in periodic manufacturing changes reports rather than supplements. These reports follow specific guidance and typically do not require Form 0356h.

Comparability Protocols: When FDA approves a comparability protocol, subsequent changes meeting the protocol criteria may be reported without a traditional supplement or Form 0356h. The protocol itself specifies reporting requirements.

The key principle: Form 0356h is required when FDA regulations mandate a formal application form for the submission type. Always consult the relevant CFR sections and product-specific guidance to confirm requirements.

Field-by-Field Requirements: Completing Form 0356h Correctly

Form 0356h contains 37 numbered fields plus continuation pages for establishments and cross-references. Each field serves a specific regulatory function. Errors in any field can trigger information requests or RTF actions.

Fields 1-6: Applicant Information

Field 1 (Date of Submission): Enter the date you submit the application to FDA in MM/DD/YYYY format. This date must match the date on your cover letter. Mismatches create confusion about filing date calculations.

Critical Detail: If you physically ship media to FDA on January 15 but the cover letter is dated January 14, this mismatch may trigger questions about whether you met a PDUFA commitment date. Always align these dates precisely.

Field 2 (Name of Applicant): Enter the legal entity name as it appears in your business registration documents. This should match exactly with the name on your DUNS registration and tax documents. For foreign applicants, use the official English translation of your company name.

Mistake to Avoid: A subsidiary company submits an application using the parent company name because the parent holds the IND. FDA’s system shows no approved applications under this name, creating delays in processing. Use the actual legal entity responsible for the application, then clarify the relationship to the parent in correspondence.

Field 3 (Telephone Number): Include the complete telephone number with country code if outside the US. Format: +[country code] [area code] [number]. This number should reach someone who can respond to urgent FDA inquiries during the filing review period.

Field 4 (Facsimile Number): Include fax number with country code. Although FDA increasingly uses electronic communication, fax numbers remain required fields. If your company no longer maintains fax infrastructure, provide an email-to-fax service number.

Field 5 (Applicant Address): Provide the complete street address including apartment/suite/unit/building/floor details in the first line, city, state, ZIP code, and country. For foreign applicants, ensure the address format follows local conventions but is clear for FDA processing.

Field 6 (US Agent Information): Foreign applicants must designate a US agent who can respond to FDA inquiries and accept service of process. This requirement appears in 21 CFR 314.80 for drugs and 21 CFR 601.2 for biologics. Include complete contact information for the US agent including name, title, address, DUNS number, telephone, fax, and email.

US Agent Mistake: A European biologic manufacturer lists a regulatory consultant as the US agent but fails to confirm the consultant has proper authorization and can legally accept service. FDA attempts to serve a notice of hearing regarding a compliance matter, but service fails because the consultant closed their practice. The resulting delay in legal proceedings costs months and creates enforcement complications.

Fields 7-15: Product Description

Field 7 (Application Number): For supplements and amendments to existing applications, provide the six-digit application number. For numbers less than six digits, precede with zeros (NDA 012345). For new original applications, leave blank—FDA assigns the number.

Field 8 (Supplement Number): For supplements, provide the four-digit supplement number preceded by zeros for numbers less than four digits. Original applications leave this blank.

Field 9 (Submission Type/Number): This field links to Field 21 identifying what type of submission accompanies the form. Examples: “Efficacy Supplement,” “Prior Approval Supplement,” “Original BLA.”

Field 10 (Applicant Serial Number): Optional tracking number for the applicant’s internal records. Use if your quality management system requires tracking submissions by internal identifier.

Field 11 (Proprietary Name): The brand name or trade name for the product. If none exists (generic products), enter “None.” Include any suffixes like XR or LA that distinguish formulations.

Proprietary Name Example: For an extended-release formulation of metformin marketed as “GlycoControl XR,” enter “GlycoControl XR” in Field 11 to distinguish it from immediate-release “GlycoControl” tablets.

Field 12 (Established Name/Proper Name): The generic or established name as recognized in official compendia or by FDA. For biologics, this is the proper name assigned by FDA. Examples: “metformin hydrochloride” for a drug, “pembrolizumab” for a biologic.

Field 13 (Dosage Form): Specify the pharmaceutical dosage form using standard terminology from FDA’s Data Standards Manual. Examples: tablet, capsule, injection, solution, suspension, cream, patch. Be specific about special characteristics: “tablet, film-coated, extended-release” rather than just “tablet.”

Field 14 (Strength): Express the strength in standard units (mg, g, mg/mL, etc.). For combination products, list all active ingredients with strengths separated by slashes: “500 mg/12.5 mg” for a two-component tablet.

Strength Specification Mistake: An ANDA lists strength as “5%” for a topical cream without specifying w/w or w/v. FDA issues an information request asking for clarification, delaying the filing decision by two weeks.

Field 15 (Route of Administration): Specify how the product is administered using standard terminology: oral, intravenous, subcutaneous, topical, ophthalmic, intramuscular, transdermal, inhalation, etc. Use the route terms from FDA’s Data Standards Council terminology.

Multiple Routes: If a product is approved for multiple routes (a drug that can be given IV or IM), list both routes separated by commas: “intravenous, intramuscular.”

Fields 16-20: Application Type and Regulatory Basis

Field 16 (Application Type): Check exactly one box: NDA, BLA, or ANDA. This determines which regulatory pathway and CFR sections apply to your application.

Field 17 (If NDA, identify type): NDAs split into 505(b)(1) applications relying entirely on the applicant’s own data or 505(b)(2) applications relying partially on published literature or FDA’s previous findings for another approved drug. The choice has profound implications for what patent certifications you must make and what data you must submit.

505(b)(2) Strategy: A company develops a new formulation of a known drug using a novel delivery system. Rather than repeating all safety and efficacy studies, the company submits a 505(b)(2) NDA relying on FDA’s finding of safety for the approved drug while submitting new bioequivalence data showing the novel formulation achieves similar exposure. Field 17 checks “505(b)(2)” and Field 20 identifies the relied-upon listed drug.

Field 18 (If BLA, identify type): BLAs split into 351(a) applications for stand-alone biologic products and 351(k) applications for biosimilar or interchangeable products. 351(k) biosimilar applications rely on FDA’s licensure of the reference product, similar to the ANDA concept for biologics.

Field 19 (If 351(k), identify reference product): For biosimilar applications, provide the proper name of the biological reference product and the holder of the licensed application. Example: “Bevacizumab; Genentech, Inc.” This information allows FDA to immediately understand what reference product provides the basis for your biosimilar claim.

Field 20 (ANDA or 505(b)(2) basis): For ANDAs, provide the name and application number of the reference listed drug from FDA’s Orange Book. For 505(b)(2) NDAs, list all drugs you are relying upon with their application numbers. Include patent certification information (Paragraph I, II, III, or IV).

Patent Certification Complexity: An ANDA for a three-strength generic product relies on an NDA with patents covering only the highest strength. The ANDA includes Paragraph III certifications for patents on the highest strength (acknowledging the patents and stating the generic will not market until expiration) and Paragraph IV certifications for other patents (claiming they are invalid or not infringed). Each certification must be accurately reflected in Field 20 and the detailed patent certification section of the ANDA.

Fields 21-23: Submission Classification

Field 21 (Select one or more submission types): This critical field identifies what types of information your submission contains. Multiple selections are allowed when appropriate (an efficacy supplement might also check CMC if manufacturing changes support the new indication).

Options include:

• Original Application (original NDA, ANDA, or BLA)
• Prior Approval Supplement
• Efficacy Supplement
• CMC Supplement
• Labeling Supplement
• Annual Report
• Periodic Safety Report
• REMS Supplement
• REMS Assessment Report
• REMS Assessment Methods and Study Protocols
• Other (with specification)

Field 21 Mistake: A sponsor submits what they characterize as a “CMC supplement” but checks “Prior Approval Supplement” without also checking “CMC Supplement.” FDA’s document room routes the submission for filing review as a PA supplement of unknown type, causing delays in assignment to the appropriate chemistry review team.

Field 22 (Submission Sub-Type): Further classify your submission as presubmission, initial submission, amendment, or resubmission. This tells FDA whether they should create a new review file or add to an existing file.

Field 23 (If supplement, identify category): Supplements are categorized by how quickly they can be implemented:

• Prior Approval (PA) – Must receive FDA approval before implementing
• CBE-30 – Changes being effected in 30 days
• CBE – Changes being effected (immediate implementation in certain cases)
• Annual Report
• Other

The category determines FDA’s review timeline. PA supplements go through full review with 6-month or 10-month PDUFA clocks. CBE-30 supplements can be implemented 30 days after submission unless FDA notifies you otherwise.

Fields 24-26: Product Characteristics

Field 24 (Indication for Use): For original applications and efficacy supplements, provide the proposed indication(s) for use. Indicate if the indication is for a rare disease (prevalence <200,000 US patients). If the product has an Orphan Drug Designation, provide the six-digit designation number.

The indication statement should align with what appears in your proposed labeling. Discrepancies between Field 24 and the actual indication in your draft prescribing information create confusion during review.

Field 25 (Combination Product Information): Identify if the product is a combination product under 21 CFR 3.2(e) by checking Yes or No. If Yes, enter the type number:

1. Convenience Kit or Co-Package
2. Prefilled Drug Delivery Device/System
3. Prefilled Biologic Delivery Device/System
4. Device Coated/Impregnated with Drug
5. Device Coated with Biologic
6. Drug/Biologic Combination
7. Separate Products Requiring Cross Labeling
8. Possible Combination Based on Cross Labeling
9. Other Type (specify)

Combination Product Example: A prefilled syringe containing a monoclonal antibody represents a biologic-device combination product. Field 25 checks “Yes” and enters “3” for Prefilled Biologic Delivery Device/System. This information alerts FDA that coordination between CBER biologic reviewers and CDRH device reviewers may be needed to assess the delivery system safety and compatibility with the biologic formulation.

Field 26 (Proposed Marketing Status): Check whether the product will be prescription (Rx) or over-the-counter (OTC). Indicate if the submission includes only pediatric data and whether Digital Health Technology data is included.

Field 27: Reasons for Submission

Field 27 is a free-text box explaining why you are submitting this application or supplement. For original applications, summarize the clinical development program and the unmet medical need. For supplements, explain what changes are proposed and why.

Example for Efficacy Supplement: “This efficacy supplement seeks approval of a new indication for use of DRUGNAME in pediatric patients ages 6 to 17 years with moderate to severe disease, based on two randomized, double-blind, placebo-controlled trials (Studies ABC-301 and ABC-302) demonstrating safety and efficacy in this population. The proposed indication would address an unmet need as no therapies are currently approved for this age group.”

Example for CMC Supplement: “This Prior Approval CMC supplement adds a second drug substance manufacturing facility located in Singapore (FEI number 1234567890) to provide redundancy and increased capacity. All specifications, release testing, and control strategy remain unchanged from the approved application.”

Field 28: Establishment Information

Field 28 represents the most error-prone section of Form 0356h. Common discrepancies observed in Field 28 account for the majority of information requests FDA issues during filing reviews.

For each facility involved in drug substance or drug product manufacturing, packaging, or testing, you must provide:

• Facility name
• Facility address
• FEI number (FDA Establishment Identifier)
• DUNS number (Data Universal Numbering System)
• Facility status: Active, Pending, or Withdrawn
• Whether facility is new to this application: Yes or No
• Whether facility is involved in the change described in this supplement: Yes or No (supplements only)
• Contact person with phone, fax, and email
• Manufacturing steps and/or type of testing performed
• Inspection readiness date

FEI vs DUNS Confusion: FEI numbers are 10-digit identifiers assigned by FDA to track establishments for inspection purposes. DUNS numbers are 9-digit identifiers assigned by Dun & Bradstreet for business identification. Common mistakes include listing the DUNS number in the FEI field or vice versa, or listing a DUNS number that does not match FDA’s database for that facility.

Facility Status Requirements:

• Active – Facility was previously approved and remains in use
• Pending – Facility is new or awaiting FDA inspection and approval
• Withdrawn – Facility is being removed from the application

Critical Rule: When submitting a supplement, facilities previously approved should be marked “Active” not “Pending.” Leaving approved facilities marked as Pending causes FDA to question whether those facilities require re-inspection, delaying approval.

New to Application Field: Check “Yes” only when introducing a facility that has never appeared in any prior submission for this application number. If adding a facility that was in the original application but withdrawn in a previous supplement, check “No” because FDA has historical information about that facility.

Inspection Readiness: Indicate when the facility will be ready for FDA inspection. For existing approved facilities, the date should be immediate or recent past. For new facilities, provide a realistic date that allows FDA to schedule inspection. Premature inspection readiness dates cause problems when FDA arrives for inspection before the facility completed validation.

Manufacturing Steps Description: Be specific about what each facility does. Generic descriptions like “manufacturing” provide no value. Better examples:

• “Final dosage form manufacturing, primary and secondary packaging, stability testing”
• “Drug substance synthesis, purification, crystallization”
• “Release testing including identity, assay, dissolution, impurities”
• “Stability testing only”

Field 29: Cross References

List all related INDs, DMFs (Drug Master Files), BMFs (Biologic Master Files), NDAs, ANDAs, BLAs, and medical device submissions (PMAs, 510(k)s, IDEs) referenced in your current application. This allows FDA to pull relevant files for reviewer access.

DMF Reference Requirements: When your application relies on a Drug Master File for excipient information, API manufacturing details, or packaging materials, Field 29 lists each DMF number. Your submission must include a Letter of Authorization from the DMF holder granting FDA permission to reference the confidential information in that DMF during review of your application.

Field 30: Submission Contents Checklist

Check all items that apply to indicate what types of information are included in your submission. This 20-item checklist covers:

• Index/Table of Contents
• Summary (e.g., Summary of Nonclinical Studies, Clinical Summary)
• CMC section
• Nonclinical pharmacology section
• Nonclinical toxicology section
• Human pharmacokinetics and bioavailability
• Microbiology (anti-infective drugs)
• Clinical data
• Safety update report
• Statistical sections
• Case report forms/Case report tabulations
• Patent information
• Patent certification
• Establishment description
• Debarment certification
• Field copy certification
• User Fee Cover Sheet
• Financial disclosure/certification
• Other (specify)

Completeness Principle: Check all applicable items. Missing checks for sections you included may cause document room staff to question whether the submission is complete. Checking items you did not include will definitely cause problems when reviewers cannot find the indicated sections.

Fields 31-37: Applicant Signature and Certification

Field 31 (Authorized Official): Enter the name of the person legally authorized to submit applications on behalf of the company. This is typically a senior executive officer, regulatory affairs vice president, or designated authorized representative.

Field 32 (Title): The authorized official’s title. Common titles include President, Vice President of Regulatory Affairs, Authorized Representative, CEO, or Attorney.

Fields 33-35 (Contact Information): Phone, fax, and email for the authorized official.

Field 36 (Date Signed): Date the authorized official signs the form. This should match or closely precede the submission date in Field 1.

Field 37 (Signature): The authorized official must sign the form. This signature represents a legal certification that the information is accurate and that the applicant agrees to comply with regulatory requirements including safety reporting, inspection cooperation, and responses to FDA information requests.

Electronic Signature Requirements: For eCTD submissions, FDA accepts electronic signatures that comply with 21 CFR Part 11. The signature must be unique to the individual, verifiable, and meet federal electronic signature standards.

Common Mistakes That Trigger RTF and Information Requests

FDA reviewers encounter recurring errors in Form 0356h submissions. Analysis of Generic Drug Forum presentations identified the top 10 most common discrepancies.

Mistake 1: Not All API Facilities Listed

The Error: The application lists drug product manufacturing facilities but omits one or more active pharmaceutical ingredient manufacturing sites, either on Form 0356h or in Module 3.2.S (drug substance section).

Why It Happens: Complex supply chains involve multiple API manufacturers including primary synthesis sites and secondary facilities performing purification or micronization. Sponsors sometimes list only the final API manufacturer assuming intermediate steps are covered under a DMF.

The Consequence: FDA issues an information request identifying the missing API facility. This delays the review cycle and may require a filing review extension. If the missing facility represents a critical control point for impurity removal or particle size control, the deficiency could be deemed not easily correctable and result in RTF action.

How to Fix It: Create a manufacturing flow diagram showing every facility that touches drug substance from starting materials through final API. Include:

• Raw material suppliers if they perform synthesis (not just warehousing)
• Primary synthesis facilities
• Purification facilities
• Micronization or particle engineering facilities
• Intermediate storage facilities if they perform any testing
• Final API testing laboratories

List each facility in Field 28 with specific manufacturing steps. Cross-reference to Module 3.2.S where detailed manufacturing information appears.

Mistake 2: FEI Number Lists DUNS and Vice Versa

The Error: The 10-digit FEI number appears in the DUNS field, and the 9-digit DUNS number appears in the FEI field, creating transposed data.

Why It Happens: Both numbers are facility identifiers, causing confusion about which belongs where. Companies copying from previous submissions may paste numbers into wrong fields without verification.

The Consequence: While FDA characterizes this as a “minor administrative error,” it still triggers mandatory information requests to clarify and update. Every information request extends review timelines and creates additional work for both sponsor and FDA.

How to Fix It: Before submission, verify every facility’s FEI and DUNS numbers against FDA’s database. The FDA Data Dashboard provides lookup tools where you can confirm:

• FEI numbers (10 digits) – obtained through FDA establishment registration
• DUNS numbers (9 digits) – obtained from Dun & Bradstreet

Create a master facility table in your internal quality system that lists both numbers for each facility. Require independent verification by a second person before finalizing Form 0356h.

Mistake 3: Previously Approved Facilities Still Checked Pending

The Error: A facility that received FDA approval months or years ago remains marked with “Pending” status in subsequent supplements or annual reports. Alternatively, withdrawn facilities remain checked as “Withdrawn” rather than being removed from the form.

Why It Happens: Sponsors use a previous Form 0356h as a template without updating facility status fields. The quality management system does not trigger a review of establishment status before each submission.

The Consequence: FDA reviewers see conflicting information suggesting facilities may need re-inspection. This prolongs evaluation while FDA confirms inspection status in their internal databases. If reviewers miss the discrepancy, scheduling systems may queue unnecessary pre-approval inspections.

How to Fix It: Implement a procedure that requires reviewing every facility status in Form 0356h against the most recent FDA approval letter. When FDA approves a supplement, immediately update your master facility list to change “Pending” to “Active.” For withdrawn facilities, remove them entirely from Form 0356h once FDA acknowledges the withdrawal in an approval letter.

Mistake 4: Facilities Marked Withdrawn But No Reference on Cover Page

The Error: Field 28 shows a facility checked as “Withdrawn” but the cover letter and Field 27 contain no explanation of the withdrawal or reference to when the withdrawal was requested.

Why It Happens: Companies mark facilities as withdrawn when submitting a supplement that removes a facility, but they fail to explicitly state in the cover letter and reasons for submission that a facility withdrawal is part of the submission.

The Consequence: FDA reviewers may overlook the withdrawal request embedded in Field 28, resulting in the facility remaining in FDA’s active records for that application. The facility continues to appear on inspection lists and compliance monitoring dashboards.

How to Fix It: When withdrawing a facility, address it prominently in three places:

1. Cover letter first paragraph: “This supplement withdraws the drug product packaging facility in Location X (FEI 1234567890) and adds a new packaging facility in Location Y (FEI 0987654321).”
2. Field 27: “This CMC supplement withdraws the packaging facility in Location X and substitutes the new facility in Location Y, which uses identical packaging equipment and procedures.”
3. Field 28: Mark the Location X facility with “Withdrawn” status.

This triple redundancy ensures FDA document room staff and scientific reviewers all see the facility change.

Mistake 5: Facilities on 0356h Not Reflected in Module 3 and Vice Versa

The Error: A facility appears on Form 0356h but is not mentioned in Module 3 (drug substance or drug product sections), or Module 3 describes manufacturing at a facility not listed in Field 28.

Why It Happens: Different people prepare Form 0356h and Module 3, working from separate templates. Changes made to one document do not flow through to the other. Last-minute facility changes update Module 3 but sponsors forget to update Field 28.

The Consequence: FDA issues a facility information request asking you to update Field 28 and corresponding Module 3 sections to reconcile the discrepancies. In complex cases, FDA may place the application on hold until discrepancies are resolved, especially if the missing facility appears critical to manufacturing or quality control.

The Rule of Thumb: Not all facilities in Module 3 need to appear on Form 0356h, but the reverse is true. All facilities on Form 0356h should be included in Module 3. The distinction: Module 3 may include research and development facilities that generated data supporting the application, but those facilities do not need to be on Form 0356h if they will not perform commercial manufacturing. However, every facility listed on Form 0356h must have corresponding detailed information in Module 3.2.S (for drug substance sites) or Module 3.2.P (for drug product sites).

How to Fix It: Create a comparison matrix listing:

• Column 1: All facilities on Form 0356h with FEI numbers
• Column 2: Module 3 location where each facility is described (section number)
• Column 3: Verification checkmark by quality assurance

This matrix should be signed off by both the person preparing Form 0356h and the person preparing Module 3 to ensure alignment.

Mistake 6: Incomplete Facility Information

The Error: Form 0356h lists a facility but provides incomplete information such as missing DUNS number, no contact person, vague manufacturing steps like “testing” without specificity, or blank inspection readiness date.

Why It Happens: Information collection from manufacturing partners proceeds slowly, and sponsors submit applications with incomplete data planning to provide details in an amendment. Foreign contract manufacturing organizations may resist sharing proprietary information or be unfamiliar with FDA requirements.

The Consequence: FDA cannot schedule pre-approval inspections without complete facility information. The filing review may identify incomplete establishment information as a deficiency. If the deficiency is not easily correctable within the 60-day filing window, FDA may refuse to file the application.

How to Fix It: Establish contractual requirements in agreements with all manufacturing partners specifying they must provide complete FDA registration information including:

• Official facility name registered with FDA
• Complete address in local format
• Current FEI number (if facility does not have one, it must register with FDA)
• Current DUNS number
• Primary contact person who can coordinate FDA inspections (name, title, phone, email)
• Detailed manufacturing steps performed
• Testing capabilities and types of tests conducted
• Current inspection readiness status

Collect this information at least 60 days before planned submission. If any manufacturing partner cannot provide required details by this deadline, delay the submission rather than submitting incomplete data.

Mistake 7: Supplement Includes Unrelated Facility Change

The Error: A supplement addressing one issue (for example, a labeling change) includes in Field 28 a facility marked “Yes” for “Is the establishment new to this application?” even though the new facility is unrelated to the supplement’s subject matter.

Why It Happens: Companies try to add facilities opportunistically to approved applications by embedding the new facility in an unrelated supplement, hoping to avoid submitting a separate Prior Approval supplement focused solely on the facility addition.

The Consequence: FDA treats this as a separate facility addition requiring its own review, potentially converting what should have been a simple labeling supplement into a complex CMC supplement. The submission may be routed to the wrong review division or placed in the wrong review queue, causing delays.

How to Fix It: Submit facility changes in appropriate supplement types. If adding a new manufacturing facility, submit a Prior Approval CMC supplement specifically addressing the facility addition with complete manufacturing and control information. Do not embed facility changes in labeling or annual report submissions unless the facility change directly relates to the subject of that submission.

For supplements where existing facilities are involved, use the field “Is the establishment involved in the change described in this supplement?” correctly:

• Check Yes if the facility performs work related to the supplement (for example, a facility implements a revised analytical method proposed in a CMC supplement)
• Check No if the facility continues unchanged (for example, a labeling supplement does not affect manufacturing, so all facilities check “No”)

Mistake 8: Missing API/Facility Combination Fee

The Error: For ANDA submissions including API manufacturing information other than by reference to a Type II DMF, the applicant fails to pay the Section 744B(a)(3)(F) fee which relates to API and facility combinations under GDUFA.

Why It Happens: The fee structure is complex. Applicants assume that paying the base ANDA fee covers all requirements without realizing that providing API manufacturing information directly in the ANDA (rather than referencing a DMF) triggers an additional facility fee for each API facility.

The Consequence: FDA refuses to receive (RTR) the application until the user fee deficiency is corrected. Unlike an RTF action issued after filing review, an RTR occurs immediately upon submission when user fee issues are detected. The application returns to the sponsor without a PDUFA date.

How to Fix It: When preparing the GDUFA user fee cover sheet (Form FDA 3794), carefully answer questions about API manufacturing information. If your ANDA includes direct API manufacturing details in Module 3 rather than referencing a DMF, you must pay the additional API/facility combination fee. The FDA User Fee System calculates the correct fee based on your answers to questions about facilities and DMF references.

Always include a copy of the completed user fee cover sheet in the first volume of your ANDA immediately after Form 0356h. This allows FDA document room staff to verify that fees were paid before assigning the application for review.

Mistake 9: Inconsistent Application Type Selection

The Error: Field 16 checks one application type (for example, NDA) but Field 17 or Field 18 contains selections for a different application type, or Field 21 submission type conflicts with the application type.

Why It Happens: Forms are incompletely filled out with selections copied from previous submissions without clearing irrelevant fields.

The Consequence: FDA routing systems rely on Field 16 to direct applications to the correct center and division. Conflicting information causes routing errors, sending applications to the wrong review team and delaying assignment by weeks.

How to Fix It: Treat Fields 16-20 as a decision tree where each selection determines which subsequent fields are required:

• If you check NDA in Field 16 → complete Field 17 (505(b)(1) or 505(b)(2)) and Field 20 if 505(b)(2)
• If you check BLA in Field 16 → complete Field 18 (351(a) or 351(k)) and Field 19 if 351(k)
• If you check ANDA in Field 16 → complete Field 20 with RLD information

Leave all non-applicable fields blank. Before finalizing the form, verify that only relevant fields contain data.

Mistake 10: Wrong Supplement Category Selected

The Error: Field 23 selects Prior Approval supplement, but the changes described in Field 27 and the supplement content meet the criteria for CBE-30 or Changes Being Effected, resulting in submission of an unnecessarily restrictive supplement type.

Why It Happens: Sponsors default to Prior Approval when uncertain about categorization, believing it is “safer” to seek approval before implementing changes. However, this conservative approach delays implementation of beneficial changes and wastes FDA review resources.

The Consequence: The company waits 6 months or more for FDA approval of changes that could have been implemented in 30 days under CBE-30 or immediately under CBE. Competitors gain market advantage by implementing similar changes more quickly.

How to Fix It: Consult 21 CFR 314.70 for drugs and 21 CFR 601.12 for biologics, which specify exactly what changes fall into each supplement category. FDA guidance documents for specific product types provide additional clarity. Examples:

Prior Approval required: New indication, new dosage form, change to sterile manufacturing site, relaxing specifications

CBE-30 allowed: Manufacturing process changes within approved parameters, certain equipment changes, editorial labeling corrections to fix errors

CBE allowed: Changes to comply with official compendia, emergency labeling changes to add new safety information

When uncertain, submit a controlled correspondence to FDA asking whether a proposed change requires PA or can be submitted as CBE-30. FDA typically responds within 60 days, clarifying the appropriate pathway.

Special Scenarios and Nuanced Requirements

Several situations require modified approaches to Form 0356h completion beyond the standard field-by-field instructions.

Grouped Supplements

FDA allows sponsors to group certain CMC changes into a single supplement under specific conditions. All proposed changes must:

• Be the same change type (for example, all manufacturing site changes)
• Be submitted as the same supplement category (all PA or all CBE-30)
• Have the same submission date on Form FDA 356h
• Be scientifically related such that reviewing them together makes sense

Example: A company manufactures a tablet at three facilities and seeks to implement identical process improvements at all three sites. Rather than submitting three separate CMC supplements, the sponsor groups the changes into one supplement with Form 0356h listing all three facilities and explaining that each will implement the same process parameter change.

The benefit is administrative efficiency and consistent review standards. FDA evaluates the change once and applies the decision to all facilities simultaneously.

Combination Products: Navigating Multi-Center Review

Combination products that pair drugs with devices or biologics with devices undergo review by more than one FDA center. The primary mode of action determines the lead center, but the non-lead center consults on its constituent part.

Drug-Led Combination Product: A prefilled autoinjector containing a drug solution has the drug as the primary mode of action. CDER serves as the lead center, and CDRH provides device review consultation. Form 0356h checks “NDA” in Field 16 and “Yes” for combination product in Field 25 with type “2” (Prefilled Drug Delivery Device/System).

Device-Led Combination Product: A drug-eluting stent has the device as the primary mode of action (physically opening the artery), with the drug serving a secondary role (preventing restenosis). CDRH leads the review as a medical device submission, and CDER consults on drug constituent part. This submission uses device forms (not Form 0356h), but if the drug constituent later needs changes, a supplemental NDA-type submission to CDRH may require Form 0356h for the drug component.

Critical Detail: The Office of Combination Products makes binding determinations about which center leads review through the Request for Designation process. Submitting your application to the wrong center because you misjudged primary mode of action creates substantial delays as FDA transfers files between centers.

Manufacturing Changes in Expedited Programs

Products under expedited development programs (Breakthrough Therapy, Fast Track, Accelerated Approval, Priority Review) face unique timing pressures. Manufacturing often continues to evolve during review cycles.

Rolling Review Considerations: Breakthrough Therapy and Fast Track designations allow rolling submission where you submit completed sections before the entire application is finished. Each module submitted includes Form 0356h, but the establishment information evolves as you finalize manufacturing arrangements.

Initial Module 3 submission: Form 0356h lists planned commercial manufacturing sites marked as “Pending” with estimated inspection readiness dates 6-9 months in the future. Manufacturing steps describe planned processes based on pilot-scale development.

Updated CMC submission before approval: An amendment updates Form 0356h facility information with final site designs, actual inspection readiness dates, and revised manufacturing procedures based on process validation results.

The key is transparency. FDA expects facilities to be ready for inspection before approval, so submit Form 0356h updates as information solidifies rather than waiting until the last moment.

Biosimilar and 351(k) BLA Considerations

Biosimilar applications under Section 351(k) of the PHS Act rely on FDA’s finding of safety and effectiveness for the reference product, similar to how ANDAs rely on reference listed drugs. However, biosimilars face additional complexity because biologics are not identical copies—they are “highly similar” with no clinically meaningful differences.

Field 19 Specificity: When completing Field 19 for a 351(k) application, provide the exact proper name of the reference product as FDA assigned it and the exact name of the license holder. Minor variations create ambiguity. If the reference product is “adalimumab” manufactured by AbbVie Inc., do not write “Humira” or “AbbVie” without the full proper name and corporate entity name.

Analytical Similarity Data: Biosimilar applications include extensive analytical data comparing the proposed biosimilar to the reference product. Form 0356h Field 30 must check appropriate boxes for all sections included: nonclinical pharmacology, clinical pharmacokinetics, clinical data, and statistical sections. Omitting any checkbox for sections actually included suggests incompleteness.

Rare Disease and Orphan Drug Indications

Field 24 requires indicating whether the proposed indication is for a rare disease (prevalence less than 200,000 US patients) and whether the product has Orphan Drug Designation.

Orphan Designation Timing: Companies typically request Orphan Drug Designation during IND phase, well before NDA/BLA submission. The designation provides seven years of market exclusivity upon approval. When completing Form 0356h, provide the six-digit Orphan Designation number FDA assigned when granting designation.

Rare Disease Without Orphan Designation: Some applications address rare diseases but do not have formal Orphan Designation, either because the sponsor did not request it or because FDA denied the request. Still indicate “Yes” for rare disease in Field 24 if the prevalence is below the threshold. This information helps FDA apply appropriate review standards and user fee exemptions that may apply to rare disease applications.

Pediatric Data and Special Populations

Field 26 asks whether the submission includes only pediatric data. This question applies to supplements seeking pediatric indications where the adult indication already exists under a separate approved application.

Pediatric Exclusivity Example: A branded NDA for an antidepressant is approved for adults. The sponsor conducts pediatric studies under a Written Request from FDA to gain six months of additional exclusivity. The resulting efficacy supplement includes only pediatric efficacy and safety data, so Field 26 checks “Yes” for only pediatric data. This triggers specific review procedures under pediatric use regulations.

Digital Health Technology Data: Field 26 also asks if DHT data is included. Digital health technologies include wearable sensors, smartphone apps, or remote monitoring devices that collect clinical trial data. If your efficacy supplement relies on data from patients wearing continuous glucose monitors or using smartphone-based symptom diaries, check “Yes” for DHT data. FDA provides specific guidance on DHT use in clinical trials that applies to data validation and source documentation requirements.

Strategic Do’s and Don’ts for Form 0356h Success

Mastering Form 0356h requires more than technical accuracy. Strategic preparation prevents delays and positions your application for efficient review.

Do’s: Best Practices for Efficient Submissions

Do maintain a master facility database: Create a central repository in your quality management system listing every facility your company uses for any FDA-regulated product. Include FEI numbers, DUNS numbers, complete addresses, contacts, and current status for each facility. Update this database immediately when facilities receive approval or withdraw. When preparing Form 0356h, pull data from this authoritative source rather than copying from old submissions.

Do conduct pre-submission mock reviews: Assign someone not involved in preparing the submission to review Form 0356h against Module 3 and the cover letter, checking for consistency. This person should verify:

• Every facility on Form 0356h appears in Module 3
• All FEI and DUNS numbers match FDA database records
• Facility status reflects current approval letters
• Manufacturing steps align with descriptions in Module 3 sections
• Supplement category matches the changes described

Do use FDA validation tools: FDA provides eCTD validation tools that check technical compliance with electronic submission standards. Run your submission through these validators before sending to FDA. The tools identify formatting errors, missing files, and broken links that would cause technical rejections.

Do verify inspection readiness before listing dates: When providing inspection readiness dates in Field 28, confirm with site quality assurance that validation studies are complete, procedures are finalized, and the facility can actually support an FDA inspection on that date. Providing premature readiness dates causes embarrassment and delays when FDA arrives for inspection and finds incomplete facilities.

Do align user fee cover sheets with Form 0356h: The PDUFA cover sheet (Form FDA 3397), GDUFA cover sheet (Form FDA 3794), or BsUFA cover sheet must present information consistent with Form 0356h regarding application type, facilities, and submission characteristics. Discrepancies between the forms cause user fee calculation errors and payment issues that delay filing.

Don’ts: Common Strategic Errors to Avoid

Don’t copy old Form 0356h without updating: Using a previous submission’s Form 0356h as a template is efficient, but only if you meticulously update every field. The top mistake sponsors make is copying facility information without updating status fields, leaving “Pending” facilities that have been approved or “Active” facilities that have been withdrawn.

Don’t bundle unrelated changes to save supplement fees: While FDA allows grouped supplements for related changes, trying to bundle completely unrelated changes into one supplement to avoid filing separate supplements backfires. FDA recognizes the tactic and may refuse to file applications that inappropriately combine disparate changes requiring different review expertise.

Don’t submit Form 0356h for amendment types that don’t need it: Amendments to pending applications do not need new Form 0356h submissions. Including the form creates confusion about whether you are trying to convert the amendment into a new supplement. Reserve Form 0356h for original applications, resubmissions, and supplements where FDA requires it.

Don’t rely solely on internal knowledge without FDA database verification: Your company may believe it has the correct FEI number for a contract manufacturer, but the FDA database is the authoritative source. Facilities sometimes change legal entity names, creating new registrations with new FEI numbers. Always verify against FDA’s official records before submitting.

Don’t leave fields blank that should say “None”: When a field asks for information that does not apply to your submission, affirmatively enter “None” or “N/A” rather than leaving the field blank. Blank fields create ambiguity—is the field blank because it doesn’t apply, or did you forget to complete it? Clear “None” entries eliminate this confusion.

Comparison Table: When Form 0356h Is Required vs Optional

Frequently Asked Questions

Is Form 0356h required for IND submissions?

No. Investigational New Drug (IND) applications use Form FDA 1571 as the cover sheet, not Form 0356h. Form 0356h is exclusively for marketing applications (NDAs, ANDAs, BLAs) and related supplements.

Can I submit an ANDA without complete establishment information?

No. Complete facility information is mandatory for original ANDAs under FDA guidance. Missing or incomplete establishment details in Field 28 constitutes grounds for refuse-to-file action during initial filing review.

Do all supplements require the same level of Form 0356h detail?

No. Prior Approval and Efficacy supplements require complete Form 0356h with full establishment sections. Minor supplements like labeling-only changes may use simplified forms without facility details if no manufacturing changes occur.

What happens if FEI numbers are incorrect on Form 0356h?

Information request issued. FDA sends an official information request requiring correction. This delays review and may extend the filing period. Always verify FEI numbers against FDA’s establishment database before submission.

Is Form 0356h required for REMS assessment reports?

No. REMS assessments submitted under existing REMS do not require Form 0356h. However, if the assessment accompanies a proposed REMS modification supplement, the supplement requires Form 0356h as the cover sheet.

Can I use an outdated version of Form 0356h?

No. FDA expects the most current version dated July 2023 with expiration March 2026. Using obsolete versions creates administrative deficiencies triggering information requests or filing delays.

Do amendments to supplements need new Form 0356h?

No. Amendments to supplements already under review do not require new Form 0356h. The amendment cover letter references the supplement number and original submission containing Form 0356h.

Must Form 0356h list excipient suppliers?

Generally no. Excipient suppliers do not need listing on Form 0356h unless they perform testing that impacts the control strategy. Simple procurement and warehousing do not trigger listing requirements.

Is electronic signature acceptable on Form 0356h?

Yes. Electronic signatures complying with 21 CFR Part 11 are acceptable. The signature must uniquely identify the authorized official and meet federal electronic signature standards for legal binding effect.

What if my application has no US manufacturing sites?

US Agent required. Foreign applicants with no US facilities must designate a US Agent in Field 6. The agent accepts service of process and responds to FDA inquiries on behalf of foreign applicant.

Do biosimilar applications list the reference product facilities?

No. Biosimilar applications list only the biosimilar manufacturer’s facilities, not facilities used by the reference product sponsor. Field 19 identifies the reference product name but not its manufacturing sites.

Can Form 0356h be amended after initial submission?

Yes through amendment. If you discover errors in Form 0356h after submission but before filing decision, submit an amendment with corrected Form 0356h. Explain the corrections in amendment cover letter to ensure reviewers use updated information.

Are crude heparin sites required on Form 0356h?

Yes for heparin products. All crude heparin manufacturing and testing sites must appear on Form 0356h and in Module 3. Inform FDA immediately of any crude heparin site changes through appropriate amendments or supplements.

Does Form 0356h require disclosure of clinical trial sites?

No. Field 28 establishment information covers manufacturing, packaging, and control sites only. Clinical trial sites appear in Module 5 clinical sections, not on Form 0356h.

What constitutes “complete” establishment information?

Nine required elements. Complete establishment information includes facility name, address, FEI number, DUNS number, status, contact person with phone/email, manufacturing steps or testing types, inspection readiness date, and indication whether facility is new to application.