USA

510(k) is a premarket submission made to the FDA to obtain approval to market a class I, II or III device that is not subject to a Premarket Approval Application (PMA) or unless exempt from the 510(k) requirements. Some novel devices will follow the De Novo pathway. 

510(k) submission made to the FDA will demonstrate that the device to be marketed is safe and effective and substantially equivalent to a legally marketed device.  This is the fastest and most economical way to get your product cleared. 

510(k)s are required when:

 ● Introducing a device into commercial distribution for the first time.  510(k) submission must be made 90 days prior to offering the device for sale.

 ● There is a change or modification to a legally marketed device that could significantly affect its safety and effectiveness. 

There are three types of 510(k) submissions that can made to the FDA. 

1) Traditional 510(k):

Traditional 510(k) submissions are for any original device that has not been previously cleared or for a change to a previously cleared device that does not qualify for a Special 510(k).  This submission takes 90 days to be cleared by the FDA.

2) Special 510(k): 

Special 510(k) submissions are design changes or modifications to a previously cleared device that does not affect the intended use. These submissions takes 30 days to be cleared by the FDA.

3) Abbreviated 510(k): 

Abbreviated 510(k) submissions are when a guidance document is available for a device, and/or a special control exists or declaration of conformity to special FDA recognized standards. These submission takes 90 days to be cleared by the FDA. 

In preparation for a traditional and abbreviated 510(k)s should include all 20 sections of the guidance document “Format for Traditional and Abbreviated 510(k)s. 

Special 510(k) should follow the Special 510(k) Program guidance document - Appendix A: Recommended content of a Special 510(k).

510(K) submissions will undergo an Acceptance Review prior to proceeding to a Substantive Review. 

FDA’s intent is to complete the 510(k) review within 90 days and a decision letter will be sent to the submitter.

We, at Medical Device Advice, Inc., can help you determine the classification of your device, product code, jurisdiction, predicate device, type of 510(k) submission, help you calculate the user fee and, finally prepare and submit the premarket notification on your behalf to the FDA.   

We will also interact with the FDA on your behalf and assist in responding to any additional information (AI) requests. 

Our utmost goal is to get your product cleared by the FDA in the shortest amount of time.

FDA 21CFR part 820 is a Quality System Regulation governing the current good manufacturing practices (cGMP’s)  for devices sold into the US market. It is critical for all medical device manufacturers to establish and follow quality systems to ensure that their products consistently meet applicable requirements and specifications. 

QSR requirements for medical devices were first authorized by section 520 (f) of the Federal Food, Drug, and Cosmetic Act. FDA QSR took effect in 1978 and predates ISO 13485 which was introduced in 1996. However in recent years FDA has been moving towards globalization harmonization and has made efforts to  align ISO13485:2016 with the FDA QSR. FDA’s participation in the Medical Device Single Audit Program is an indication FDA is moving towards accepting ISO 13485:2016 in its entirety. It is anticipated FDA will not abandon the QSR, however it will incorporate all  major components of the ISO13485:2016 into a revamped QSR.

There are eleven clauses on the ISO 13485:2003 standard that has significantly changed in the ISO13485:2016 standard and more in align with the 21CFR part 820 QSR.

These clauses are,

(1) Application of a risk-based approach in establishing and maintaining a QMS,

(2) Protection of confidential information and requirements to address deterioration and loss of documents,

(3) Requiring process for establishing competence, providing needed training and ensuring awareness of personnel,

(4) Communication with regulatory authorities as it relates to product information, customer feedback, complaints and advisory notices,

(5) Design and development more in alignment with QSR Design Controls,

(6)  Requirements from design and development into production,

(7) Maintaining design and development files in alignment with the Design History file requirements from the QSR,

(8) Supplier Related requirements,

(9) Documented procedures as it relates to production identification and status throughout all stages of product realization,

(10) Complaint handling,

 
(11) Reporting product issues to regulatory authorities.

We can assist you in performing a gap assessment to identify any deficiencies within your current system against the QSR requirements and help you with the implementation, training and ensure full  compliance to the QSR requirements. 

ISO 13485:2016 is the most current version of the Quality Management System (QMS) for Medical Device manufactures, which is based on the ISO 9001:2008 standard.  

On February 25, 2016, the International Organization for Standardization published the 2016 version replacing the 2003 version giving a three year transition period which ended on February 28, 2019. All Manufacturers are required to comply to this new standard as of this effective date.  

Medical Device Single Audit Program (MDSAP) is an international initiative led by five Regulatory Authorities to implement a program where MDSAP recognized Auditing Organizations (AO) can conduct a single regulatory audit of a medical device manufacturer to satisfy the relevant regulatory requirements for upto five different medical device markets:     Australia (Therapeutic Goods-Medical Devices- Regulations 2002, 236, Compilation No. 47), Brazil (RDC ANVISA 16/2013), Canada ( CMDR SOR/98-282), Japan (MHLW MO 169) and the United States (21CFR 820 QSR).

1) Brazil

-Anvisa may use MDSAP audits in lieu of a premarket inspection by ANVISA to grant ANVISA’s GMP Certificate to manufacturers intending to put medical devices of class III or IV on the Brazilian market.  

2) Canada

- Health Canada, as of January 1, 2019 will only accept MDSAP certificates for the purpose of obtaining a new (or maintaining an existing) Class II, III or IV medical device licence.

3) Japan

- Japan’s Ministry of Health, Labor and Welfare (MHLW) and Pharmaceuticals and Medical Devices Agency (PMDA)will accept MDSAP audit report in-lieu of an on-site inspection.

4) Australia

-TGA will accept the MDSAP audit reports when considering whether to issue or maintain a TGA conformity assessment certificate. 

5) United States

- U.S. Food and Drug Administration’s (FDA) Center for Devices and Radiological Health, will accept the MDSAP audit reports as a substitute for FDA routine inspections. However it does not apply to "For Cause" or "Compliance Follow-up" inspections.

We at Medical Device Advice, Inc., have experienced consultants who can evaluate your current system to determine your level of compliance to ISO 13485:2016/MDSAP and pave a pathway for a successful transition to this new standard.

In 1962, Congress instructed the FDA to amend the Food, Drugs and Cosmetic Act to add Good Manufacturing Practices. This was due to concerns about substandard drug manufacturing practices of Thalidomide, a sedative used to treat morning sickness in pregnant women, which was causing birth defects in Europe, Canada and other countries. 

In 1978, Current Good Manufacturing Practice regulation for Drugs (21CFR part 210-211) were finalized. All manufacturers of drugs are required to comply with these regulations.

21CFR part 210 contains the minimum good manufacturing practice  requirements to be used in manufacturing, processing, packing, holding of a drug so that the drugs meets the requirements of safety, identity, strength, quality and purity.  

Failure to comply with these regulations will render the drug to be adulterated and the person responsible will be subjected to regulatory action. 

This regulation will also apply to manufacturers of human cells, tissues, and cellular and tissue-based products that are considered as drugs.

21CFR part 211 is the meat of the regulations containing the minimum current good manufacturing practice for the preparation of drug products.  

There are eleven subparts identified by letters A through K, which includes, organization and personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling control,  holding and distribution, laboratory controls, records and reports, and returned and salvaged drug products. 

At Medical Device Advice, Inc., we can help you achieve and maintain compliance to 21CFR part 210 and 211.

21CFR part 1271 regulates the Good Tissue Practices (CGTPs) for human cells, tissues, and cellular and tissue-based products (HCT/Ps). 

Human cells, tissues and cellular and tissue-based products (HCT/Ps) are critical in reconstruction surgeries, wound closures and many other life-saving medical procedures. 

Current Good Tissue Practice guidelines are aimed at ensuring the safety of HCT/Ps by preventing the introduction, transmission and spread of communicable diseases. 

If you manufacture HCT/P’s that are solely regulated under section 361 of Public Health Service Act you will register and list your HCT/P with the Food and Drug Administration’s (FDA’s) Center for Biologics Evaluation and Research. 

If you manufacture HCT/P’s that are regulated as drugs, devices and/or biological products, you need to register and list your HCT/P’s following 21CFR 207 if it’s a drug or biological product or follow 21CFR 807 if it’s a medical device. 

The requirements for cGTP are found in subparts C and D of 21CFR 1271, which govern the method and controls used for manufacture of HCT/Ps. 

This includes all activities and tissue processing steps involved in the recovery, donor screening, donor testing, processing, storage, labeling, packaging and distribution of HCT/Ps.

Our consultants at Medical Device Advice, Inc., can help you implement and be compliant to 21CFR part 1271.

FDA form 483 is issued to a firm with a list of observations when the FDA inspector determines non compliance or inadequacies during an inspection of a firm. 

A warning letter is an official document issued by the FDA when it believes a company has significantly violated the FDA regulations or if the corrective and preventive action taken by the firm in response to a 483 observation is inadequate. If the FDA is not satisfied with the warning letter response from the firm, it can take further enforcement action. 

FDA can also take enforcement action without issuing a warning letter for issues such as repeated violation, adulterated product, adulterated data, gross contamination of product, more potent or less potent than what the label claims, significant violation of cGMPs, etc. 

Further enforcement action by the FDA can lead to product recalls, rejection of product approvals, and even plant shut down.

A well prepared, detailed response letter to the form 483 or warning letter addressing each non-conformity with timely implementation of the corrective and preventive action, and submission of timely follow up updates to the FDA will avoid further action by the FDA. 

We have consultants who have over 25 years of experience with all aspects of FDA inspections and compliance who can help you navigate through this process successfully. 

Establishments that are involved in the production and distribution of medical devices intended for commercial distribution in the USA are required to register annually with the FDA.  

Most establishments that are required to register also need to list the medical devices and the type of activity performed at each site. 

All registrations and listings are performed electronically unless a waiver has been provided. The renewals for each fiscal year is performed between October 1st and December 31st . 

All establishments must pay their user fee prior to completing the registration by visiting the Device Facility User Fee Website. Upon payment you will receive the confirmation numbers (PIN/PCN). Then you will proceed to the FURLS website to complete the registration and listing. 

We have experienced consultants who can help you with the FDA Establishment registration, Medical Device Listing and facilitate in obtaining U.S Agents for foreign sites.

Medical Device Reporting (MDR) requires all Manufacturers, Importers and Device User facilities to submit mandatory adverse event reports, also known as medical device reports, to the FDA in an electronic format that the FDA can process, review and archive in accordance with 21CFR part 803 Medical Device Reporting Regulations.  

An event becomes reportable to the FDA when a medical device:

 ●  May have caused or contributed to a death or serious injury,

 ●  Malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur,

For timelines on submissions, there are three types of reports that can be submitted

1. A 30-day (Initial) Report must be submitted within 30 calendar days of the firm becoming aware of a reportable device-related death or serious injury, or a reportable malfunction.

2. A 5-day Report must be submitted within 5 working days after the firm becomes aware of a reportable event that requires remedial action to prevent harm to public health or for which FDA has made a written request for the submission of a 5 day report.

* A Supplemental Report is a “supplemental” or “follow up report” that is submitted when additional information that was not available when a 30- day or 5-day report becomes available. 

Our experienced consultants can help you determine when an incident is reportable to the FDA and help submit the MDR electronically on your behalf. 

We can also assist you in developing, maintaining and implementing MDR procedures within your site and ensure compliance to the FDA requirements. 

Medical Device Recall is a removal or correction of a marketed product that is in violation of the laws administered by the FDA. Product recalls are often very challenging to manufacturers and distributors. Time is of the essence.  Any mishandling could have catastrophic consequences to customers, patients and the company. 

Recalls need to be handled competently to reduce the risk of possible injury to patients and users.  Most of the recalls are voluntarily undertaken by the manufacturers or distributors or at the request of the FDA. Once a decision has been made to recall a device, the recalling firm needs to have a recall execution team that will follow established procedures based on 21CFR part 7. 

Recalls are classified into 3 classes based on the health hazard associated with the product being recalled, the classification and the intended use of the device. 

1. Class I Recall is when use of the defective product will have serious adverse health consequences or death.

2. Class II recall is when use of the defective product having serious adverse health consequences is remote.

3. Class III Recall is when use of the defective product is not likely to cause adverse health consequences.

We can help you,

 ● Develop an effective standard operating procedure on recalling your product,

 ● Implement an efficient voluntary recall program and an effective recall strategy,

 ● Write an efficacious notification letter,

 ● Advise on whom, how and when to notify the FDA of a recall,

 ● Assist with performing an effectiveness check,

 ● Train you on how to implement corrective action for a recall, and

 ● Assist in the preparation of the recall status reports.

Section 201 of the FD&C Act distinguishes between label and labeling. Both these terms are related but not interchangeable. 

Section 201 (k) defines "label" as a display of written, printed, or graphic matter upon the immediate container of any article.

Section 201 (m) defines "labeling" as all labels and other written, printed, or graphic matter upon any article or any of its containers or wrappers, or accompanying such article. 

Of the two terms “label” is more restrictive.  It consists of the part of the display confined to the device itself. On the other hand, “labelling” deals with the label of the device, and descriptive and product literature that accompanies with the device. 

We at Medical Device Advice, Inc., can assist you with the following,

 ●  Ensure that your label is in compliance with the 21CFR 801 General Device Labeling regulations,

 ●  Review your current label or draft labels to confirm compliance to the current labeling regulations,

 ● Provide assistance in drafting  labels for 510(k) submissions,

 ●  Review marketing material or any labeling material to ensure proper claims have been made and they do not pose an unduly enforcement action by the FDA.

Due Diligence is extremely important in the pharmaceutical world as it allows the buyer to assess all aspects of a potential acquisition to determine what the benefits, risks and opportunities are. 

Not only are the detailed reviews of the business, financial and sales data are critical, but it is imperative that a thorough assessment of the firms quality and regulatory history are included in due diligence. 

In most cases, this needs to be done quickly and efficiently by an independent third party who will ensure no important elements are overlooked. 

Medical Device Advice, Inc., regulatory team will provide you with the  required information to make an unbiased assessment, understand the state of compliance and identify any potential regulatory risk associated with this merger or acquisition. 

Our due diligence service includes the following review:

 ●  GMP compliance, 

 ●  FDA regulatory or other governing body, 

 ●  SOP’s and procedures,

 ●  Complaint Handling and Recalls,

 ●  Adverse Event reporting,

 ●  Manufacturing, 

 ●  Labeling Compliance,

 ●  Post Market Surveillance.

FDA's OTC Drug Review (Developed under the OTC drug monograph process) was established in 1972 to review the safety and efficacy of OTC drug products. It is a three phase public rule making process, which resulted in the establishment of the drug monograph.

Step 1: First phase resulted in the review of the active ingredients to determine if these ingredients could be generally recognized as safe and effective. 

An advisory panel was also responsible for reviewing claims and recommending appropriate labeling. Panels conclusion were  published in the Federal Register as “Advance Notice of Proposed Rulemaking” (ANPR). 

Panel classified the ingredients into the following categories:

 ●  Category I – Generally recognized as safe and effective - GRASE

 ●  Category II – Not GRASE 

 ●  Category III – Insufficient data to determine safety and/or efficacy. 

Step 2: Following FDA review and public comment a tentative final monograph (TFM) is issued by the FDA proposing approved ingredients, uses, doses, required warnings and appropriate claims. TFMs are in place for virtually all categories of OTC drugs. 

Step 3: Publication of a final monograph (FM) setting forth allowable claims, labelling and active ingredients for OTC drugs in each class is the last phase of the review process. The FM will appear in the Federal Register and be reflected within 21 CFR Part 330 which lays out the general conditions by which OTC drugs are generally recognized as safe, effective and not misbranded. 

Drugs marketed in accordance with a final monograph can go directly to market and do not require FDA approval of a marketing application. 

We have experts who can help you determine if your products can follow the OTC monograph pathway. 

Our consultants can also assist you in determining the ideal product monograph for your product and also review allowable ingredients and label claims. 

If you are a foreign establishment who imports or offer for import into the United States, you are required by law to appoint a US FDA agent.

A US agent must reside in the US or maintain a place of business in the US and assume the following responsibilities:

 ●  Assist the FDA in communicating with the foreign establishment,

 ●  Communicate with the foreign establishment on obtaining information on the medical device imported into the USA,

 ●  Schedule inspections of the foreign facility in the event FDA is unable to reach the foreign facility, 

 ● Act as the intermediary between the foreign establishment and the FDA.

Information on a foreign establishment’s US agent is submitted electronically using the FDA FURLS systems during the registration process whereby, the US agent identified will confirm to the FDA that they have agreed to act as the US agent on behalf of the firm.

We can provide US Agent services to foreign establishments to facilitate establishment registration and medical device listing at a very affordable price.

All products offered for entry  into the U.S must be declared to U.S Customer and Border Protection (CBP). CBP refers all FDA regulated product to FDA for review. 

Regulated products produced abroad or domestically must adhere to the same regulations by the Food and Drug Administration.  FDA decides if the products are admissible into the U.S or may refuse entry if they find the product to appear to violate any provisions of the Food, Drug and Cosmetic Act. 

Most importers choose to hire licensed customs brokers when offering goods for entry and all entry information are entered electronically using the Automated Broker Interface (ABI) program. 

At the time of the entry review process by the FDA, the imported products must be held intact and may not be distributed until a final release is granted by the FDA. 

FDA-regulated products are refused entry, if they appear or have been found to be adulterated, misbranded, or forbidden or restricted for sale. Product that do not meet the U.S requirements will be refused admission and the product must be destroyed or exported from the U.S within 90 days.

We at Medical Device Advice, Inc., can help you develop problem-solving strategies to handle FDA import alerts, detentions, refusals and any other related compliance issues.  

We can also assist you in finding licensed customs brokers, and assist you in obtaining appropriate litigation support. 

The Food and Drug Administration issued a final rule in the Federal Register on December 2013 to establish a system to adequately identify devices through distribution and use. 

This rule requires all labels to incorporate a Unique Device Identifier (UDI) unless there is an exemption or an alternative replacement. The labeler must use the FDA’s Global Unique Device Identification Database (GUDID) to submit product information.  The GUDID is a database administered by the FDA that will serve as a reference catalog for every device with an identifier. 

This rule requires the label and device package of each medical device to include a UDI that is human readable and in a form that uses automatic identification and data capture (AIDC) technology. The UDI is comprised of two components, “Device identifier” and a “Production Identifier”. Device identifier incorporates the labeler identification code and the model or part number of the device. Production identifier includes manufacturing information for that device, such as lot number, serial number, expiration date or manufacturing date. 

Medical devices that are reprocessed or used more than once needs to have the UDI marked directly on the device. This rule will improve patient safety by reducing medical errors, more accurate reporting of adverse events so problem devices can be pinpointed, facilitate rapid recalls, prepare for medical emergencies and disasters and provide a global secure distribution chain.

We at Medical Device Advice Inc, have consultants who can help you in constructing and uploading a device attribute data sheets, label standardization, data entry into the GUDID data base and develop compliance processes and procedures for compliance to this rule.