FDA Consulting - INGENES

Commercializing your medical device or IVDs in the US market requires submitting registration applications to the US Food and Drug Administration (FDA). The content of your FDA submission depends largely on how your medical device or IVD is classified according to the agency’s classification scheme. Class I, Class II and Class III categories can entail different FDA registration requirements for medical devices. Here is a brief overview.

In instances where a medical device is difficult to classify due to new technology and intended use, Ingenes can conduct a formal classification request known as a 513(g) submission to the FDA on your behalf. Once the FDA confirms or determines the classification of your device, we can proceed with your FDA submission.

As the US Food and Drug Administration’s medical device and IVD review process becomes more complicated, partnering with an experienced FDA consultant can make a significant difference in your market authorization and compliance efforts.

The US Food and Drug Administration's Center for Devices and Radiological Health (CDRH) enforces a three-tier regulatory system for medical devices based on risk. Medium-risk devices typically require 510(k) Premarket Notification to be sold in the US, while high-risk devices must go through the Premarket Approval (PMA) process prior to commercialization. Most manufacturers must also meet quality system requirements laid out in 21 CFR Part 820 to market their devices in the US.
Let Ingenes assist you in evaluating the US medical device regulatory framework as it applies to your device(s)

Ingenes worldwide network of consultants, industry sources, and regulatory contacts enables us to develop in-depth and accurate analysis of medical device markets, including the USA. Depending on your needs, our Global Regulatory Overview report service for the U.S. medical device market covers topics such as:

Please contact us for more information about our Regulatory Overview and Regulatory Strategy Support to market your medical device in United States.

Unlike the rules-based classification schemes used in Europe and other markets, medical devices in the US are classified using a predicate-based system. The US Food and Drug Administration (FDA) uses this system to classify medical devices as Class I, II or III based on increasing risk to the patient or user.

In most cases, you can determine the correct classification of your medical device by referencing the FDA’s classification database and reading the descriptions of devices that are “Substantially Equivalent” to yours. Once you have a match, you will be able to determine the classification, three letter Product Code and the specific regulation number that will be used during the registration process. This may seem easy, but identifying the closest FDA predicate device to yours among thousands of codes is often harder than it seems.

For devices that are innovative, it can sometime be difficult to find an exact predicate device using the FDA classification database. In this case, you can submit a 513(g) “Request for Information” to the FDA. The 513(g) submission should outline the characteristics of your device and include rationale on why you believe it falls into a specific class. The FDA will evaluate your information within 60 days and issue a ruling on how your device should be classified along with a suitable regulation number and product code.

Entirely new devices are automatically considered to be Class III in the US. However, many new products are not high risk. This is why the FDA has the "de novo" process. You may consider filing a “de novo” submission if the FDA determines, through means such as a 513(g) or Pre-Submission, that your device is a “novel” with no existing classification or predicate device on the market. Within 120 days after your de novo submission, the FDA will determine if your device is Class I or II and may issue an entirely new product code and regulation number. If rejected, your device will remain as Class III.

Ingenes specializes in medical device regulatory consulting and can help you determine the proper classification for your device in the United States. Here’s how we can help:

The US Food and Drug Administration's Pre-Submission Program (Pre-Sub, formerly known as the Pre-IDE Program) allows medical device and in vitro diagnostic (IVD) manufacturers to discuss specific aspects of the regulatory process and requirements with FDA experts. A Pre-Sub is commonly referred to as a Q-Sub, as the submission to the FDA is assigned a 'Q' identification number. Ingenes experienced US consulting team has extensive expertise with the FDA Q-Sub process. We can guide you through this critical step toward FDA clearance.

How the FDA Pre-Sub process can help you achieve US market clearance for your device FDA Pre-Sub consulting is available for sponsors and manufacturers to obtain regulatory feedback on various medical device or IVD-related applications, including Investigational Device Exemptions (IDE) necessary for high risk medical device clinical investigations, premarket notification (510(k)) submissions, and clinical or non-clinical study protocols.

Topics that may be addressed using the Pre-Sub process include, but are not limited to, the following:

The FDA Pre-Sub program can prove especially valuable for devices utilizing novel technologies, or those with indications that qualify them as "first of a kind" devices.

You must formally request a Pre-Sub or Q-Sub meeting with the FDA. The contents of your Q-Sub submission for requesting a meeting should include a cover letter, a thorough description of your medical device along with its proposed intended use, the mechanism of action on the body, its technological characteristics, your planned testing strategy, and specific questions on which you are requesting input from the FDA.

You must submit your Pre-Sub meeting request before submitting your 510(k) or premarket application (PMA) review process, or before beginning a clinical study on which you are seeking feedback. There are other 'Q-Sub' meeting types that allow you to meet with the FDA for different purposes (e.g., Submission Issues meeting during the review process). However these are not as common.

The steps to a successful Pre-Sub meeting with the FDA vary somewhat by device. Ingenes can help you get the most benefit from the Pre-Sub Meeting process. Our services include:

Our consulting firm is well equipped to assist medical device and IVD manufacturers as well as study sponsors through the FDA Pre-Sub or Q-Sub process.

One of the first steps toward selling a Class II medical device or IVD in the United States is to file a Premarket Notification with the FDA, also known as an FDA 510(k) submission. Technically, the FDA does not "approve" medical devices or IVDs for sale under the 510(k) process; the agency gives "clearance" for them to be sold in the U.S. Sometimes companies use the term "FDA approval" and "FDA clearance interchangeably.

In general, manufacturers wishing to introduce Class II medical devices (and a small number of Class I and III devices) or IVDs to the US market must submit a 510(k) to the FDA. A 510(k) premarket notification is also required for manufacturers changing the intended use of their medical device, or changing the technology of a cleared device in such a way that it may significantly affect the device's safety or effectiveness.

To ensure a successful 510(k) submission, we take a two-step approach. Over the years, we have found this approach is cost-effective for our clients, and it dramatically reduces the probability of failure to receive FDA clearance of a 510(k) submission.

Step 1: Pre 510(k) submission gap analysis and requirements evaluation

Step 2: Dossier compilation and FDA 510(k) submission

When all required documents and information have been received, we will prepare your final 510(k) submission. We will:

We want you to be successful introducing your device to the US market. As a FDA consulting firm for medical devices and IVD, we have successfully prepared and submitted FDA 510(k) submissions for medical device and IVD companies from around the world seeking to sell in the United States.

Unique Device Identification (UDI) requirements for medical devices have been implemented by the US Food and Drug Administration (FDA). The FDA issued the final Unique Device Identifier (UDI) Rule and implemented into the US Federal Register on 24 September 2013.

The UDI system final rule provides standard device identification and accompanying identifying information to support various public health initiatives, including support for the FDA’s post-market surveillance (PMS) activities. Manufacturers must meet UDI requirements as part of US market compliance.

UDI compliance requires a significant effort on the part of manufacturers. Ingenes carefully followed the development of UDI rules in both the US and international markets and has the expertise and resources to help you establish compliance processes to meet US FDA UDI requirements.

FDA UDI compliance involves more than etching a number onto your medical device or adding a barcode to your label. Several components are involved.

Each UDI must contain two numbers: a Device Identifier (DI) and a Production Identifier (PI). A Device Identifier must correspond to the specific model or version of a medical device and the company name. A Production Identifier must provide a medical device’s lot or batch information or serial number, expiration date and related production data.

Manufacturers are required to submit UDI data into the FDA Global Unique Device Identification Database (GUDID) using proper formatting.

Ingenes provide comprehensive solution to support your UDI compliance efforts from beginning to end. Planning ahead allows you to identify internal resources, collect the appropriate data, and make informed decisions to ensure your firm is prepared to meet these requirements. Here’s how we can help:

Regardless of whether you are introducing a new medical device, or looking for assistance in assuring compliance for existing devices in your product portfolio, our FDA consultants can assist with UDI compliance.

Any establishment involved in the production, importation, reprocessing/relabeling, or developing specifications of a medical device or IVD for commercial sale in the United States must register annually with the US Food and Drug Administration (FDA). This is called "Establishment Registration" and it is a separate process from obtaining 510(k) clearance or PMA approval.

The medical device company must register with the FDA and pay fees to the FDA. As a general rule, if you manufacture all or part of a medical device sold in the US, or perform processing (e.g., sterilization) on the device, you must register.

With the exception of Initial Importer, FDA also requires registered establishments to list the devices. An initial importer who is responsible for furthering the marketing of a device entering the US from a foreign manufacturer to the final distributor for sale of the device to the ultimate consumer or user must register their establishment, but is not required to list the devices. Again, please refer to the table we have prepared.

Although you can complete the registration yourself using the FDA online FURLS system, some companies ask us to complete this for them as the process can be somewhat confusing. If you need assistance FDA Establishment Registration process, we can certainly help you complete the process correctly, as we have done for several medical device companies. We will:

If needed, we can also assist with assessing the classification and choosing the appropriate Product Code for your medical device, if you are registering a Class I product for the first time. In other cases, you should already have your 510(k) clearance letter, which contains the product code and other regulatory information before proceeding with FURLS registration.

Our regulatory affairs consultant coordinates all aspects of your clinical trial’s document collection and submissions, including:

According to the standard ISO 10993-1:2009, medical device material characterization as well as related material and chemical testing should be conducted prior to any biocompatibility testing. Material characterization involves evaluating the suitability of a medical device’s physical and chemical characteristics for its intended use. Furthermore, chemical and physical testing of a device’s materials is necessary for regulatory registration and compliance of many device types. Relevant standards for medical device material characterization and related testing include:

With our expertise, we can help you determine the exact regulatory requirements and types of material characterization and chemical tests for your device. Such testing usually includes chemical analysis, including tests for chemical composition, evaluations of manufacturing practices that may produce unintended extractable or leachable materials, and tests for performance characteristics like corrosion resistance, permeation rates and shelf life.

After chemical analysis, any degradable or leachable materials identified must undergo toxicological evaluation to determine any risk posed to device users and patients. In addition, your device may require physical evaluation to assess material physical strength, performance characteristic and shelf life.

It is important for medical device manufacturers to keep in mind that even after a device obtains market authorization, some regulators will require ongoing inspections of component materials, in-process controls and final product and packaging inspections. These inspections help prove that product design changes do not adversely impact biocompatibility. Also, they can help companies show that any new suppliers can meet the same manufacturing requirements as their previous suppliers, or that any retooling of suppliers’ manufacturing capabilities will not affect device materials.

Our testing methods meet ISO 10993 and related requirements, and help manufacturers meet a necessary preliminary step toward full biocompatibility testing. Our physical and chemical materials testing experts utilize multiple modern analytical procedures including GC/MS, HPLC, FTIR, ICP, XPS and SEM/EDX. Our testing services cover:

Contact us for more information on material testing and chemical analysis for your medical device.

The ISO 13485 quality system standard, and regulators in the US and Europe, require medical device manufacturers to eliminate or reduce contamination risks in their production processes that could cause infections in patients or users. For devices labeled sterile, microbiological and sterility testing are required in most major markets and you must document the results of those tests in your regulatory submission. Ingenes can help you identify the testing requirements for your sterile device and perform the necessary testing.

Sterile device manufacturers must ensure adequate and microbiologically secure manufacturing conditions, even if they outsource some or all of their manufacturing to third parties. Final sterilized products, as well as packaging materials, must often undergo additional evaluations to support sterilization claims.

Failure to complete the appropriate testing can delay the regulatory process for your device. Ingenes can help you determine the microbiology testing you need based on your device type and testing requirements in your target market.

In collaboration with our colleagues at UL, we can perform the required microbiology and sterility testing for your device. Our testing experts utilize the latest methods and equipment to assess and validate your device sterilization claims. Our microbiology tests can determine the sterilization status of your medical device, assess anti-infective properties of your device materials, and identify ways to control your manufacturing and sterilization processes.

Our microbiology and sterility testing services include:

We provide a detailed report summarizing the results of the testing. Our regulatory consultants are experts in testing requirements for US market and can help you prepare the necessary documentation for your FDA 510(k) and other submission types in markets worldwide. Our expertise in testing requirements will help you determine the exact regulatory requirements for your device.

Pre-production QMS for eventual compliance with FDA QSR and ISO 13485

Implementing and maintaining a quality management system (QMS) is a crucial part of regulatory compliance for most markets worldwide.

For small medical device manufacturers in the pre-production phase, an initial implementation of a partial quality system is an extremely beneficial way to ensure compliance with product development regulations, such as Design Controls.

As part of your QMS implementation, we will set up procedures for the following:

• Document and records control
• Training on regulatory requirements and internal procedures
• Design and development
• Risk management
• Software development (if applicable)
• Supplier evaluation
• Control of measurement equipment

US FDA Agent Representation for Medical Device and IVD Companies

The United States Food and Drug Administration (FDA) require that all medical device and IVD companies without a presence in the United States to appoint a registered US FDA Agent. The US FDA Agent must be a resident of the United States or maintain a physical place of business in the US. Your US Agent serves as a liaison between your company and the FDA.

Appointing a US Agent is more than a regulatory obligation. The responsibilities of the US Agent include:

The FDA may also provide information or documents to your US agent, which is considered equivalent to providing them to your company. For this reason, it is important to appoint a professional, dependable regulatory firm to represent your interests.

Ingenes serves as an official US Agent for medical device and IVD companies worldwide. We are compliance specialists in this field.

The Official Correspondent focuses on communication with the FDA about your establishment registration and your devices listed with the FDA. Also, the OC does not need to be located in the US. All companies selling medical devices in the US need to appoint an Official Correspondent (OC) at time of Establishment Registration. Foreign companies must appoint a US Agent, in addition to an OC. While the roles and responsibilities of a US Agent and an OC are similar, there are some key differences. The FDA defines the Official Correspondent as the person designated by the owner/operator of an establishment who is responsible for the annual registration of the establishment and the device listing. The OC also receives correspondence from the FDA involving the owner/operator and any of the firm’s establishments. The Official Correspondent is responsible for:

We have years of experience communicating with the FDA on our clients’ behalf. If engaged as your US Agent, we can also act as your Official Correspondent to the FDA.

Every foreign company registered with the FDA must appoint a US Agent who has a physical residence or place of business in the US to assist with specific FDA related responsibilities. The US Agent is responsible for FDA questions about imported devices and helps with FDA inspection scheduling, as well as communication related to the inspection.

Ingenes could handle correspondence with the FDA on your behalf. When you appoint us as your Official Correspondent and US Agent, the FDA will come directly to Ingenes for all inquiries and facility inspection notifications. We’ll ensure that your FDA communications are handled thoroughly and smoothly.

A Certificate to Foreign Government (CFG) is required by many medical device market regulators in Asia, the Middle East and Latin America in order to legally sell your product in their territories. A CFG confirms that your device has been cleared or approved for sale in the US. You can present your CFG to regulators in these markets as part of your medical device registration process. Ingenes has obtained CFG documents for many clients seeking new markets, and can procure a CFG from the US FDA on your behalf.

The US Food and Drug Administration issues CFG documents directly to companies with offices in the US. With a strong presence in the US, Ingenes has the expertise and resources to successfully procure your CFG from the FDA on your behalf.

Ingenes acts as US Agent for medical device companies that are selling their products in the US. Our US-based consulting staff can interact with the FDA on your behalf to obtain your CFG as efficiently and quickly as possible:

The FDA requires that effective May 5, 2017 all NDAs, ANDAs, and BLAs, must be submitted using eCTD format. The compliance date for Commercial INDs and DMF is May 5, 2018. It is FDA’s intent that submitted data be both compliant and useful for their reviewers. The FDA’s expectation is that, the data should conform to the applicable and required data standards. The FDA will Refuse to Receive (RTR) any submissions after May 5, 2017 that are not compliant with the eCTD submission requirements.

INGENES provides eCTD compliant writing services and can assist your company in submitting the submissions in eCTDs. There are various options for submitting documents to INGENES for conversion into eCTD format:

Once the submission is in proper form, INGENES can submit the relevant application/submission in eCTD format on your company’s behalf to FDA, or send the submission back to you to submit it to FDA through required gateway.

Please contact INGENES, if you have any questions related eCTD submission. As always, INGENES is available to review your submissions prior to sending it to FDA to ensure that the submission is complete and compliant. This will expedite your FDA’s review process, save your time, resources, money, and faster approval and get the product quickly to market.

DMF are submissions to the FDA which allow the master file holder to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing without providing proprietary information to their customers. While not required by law, the information contained within a DMF may be used to support applications such as Investigational New Drug Application (IND), a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA), another DMF, an Export Application, or amendments and supplements to any of these. Technical contents of a DMF are reviewed only in connection with the review of an IND, NDA, ANDA, or an Export Application.

INGENES Regulatory consulting prepares reviews and files DMFs on behalf of clients, ensuring that the information is complete and accurate and that all FDA regulatory requirements are met. INGENES Regulatory consulting can also provide support for any required annual updates related to master files to FDA. Of interest to foreign firms, FDA strongly encourages foreign firms to use U.S. Agents for the filing of their DMFs to ensure accuracy as well as expedited administrative review and acceptability due to familiarization with US. Laws, FDA Rules, Regulations and Guidelines. INGENES Regulatory Consulting can serve as your appointed U.S. Agent on record for the DMF.

Once the submission is in proper form, INGENES can submit the relevant application/submission in eCTD format on your company’s behalf to FDA, or send the submission back to you to submit it to FDA through required gateway.

Please contact INGENES, if you have any questions related eCTD submission. As always, INGENES is available to review your submissions prior to sending it to FDA to ensure that the submission is complete and compliant. This will expedite your FDA’s review process, save your time, resources, money, and faster approval and get the product quickly to market.

INGENES Regulatory Consulting assists clients in obtaining the necessary permissions to perform testing of Investigational New Drugs (IND) in human clinical trials as well as consult with FDA on your company’s applications. INGENES can also assist in the design of the clinical study. FDA’s role in the development of a new drug begins when the drug’s sponsor (usually the manufacturer or potential marketer), having screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans.

ININGENES has a strong history of effective communication with the FDA, and frequently function as a liaison to arrange the pre-IND meeting, end of Phase II meeting, or pre-NDA meeting and prepare meeting briefing documents. We also assist with the preparation and submission of IND amendments for protocol changes or the addition of investigators. INGENES can also assist with the Pre-IND preparation and submission, meeting request, briefing package, and meeting preparations.

At this point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of FDA’s drug regulatory system. Sponsors who are testing their Investigational New Drugs (IND) may wish to do so in multiple states, requiring an exemption to federal laws which require that drugs transported across state lines have an approved marketing application. An exemption allowing for this transportation can be sought from FDA under 21CFR Part 312 allowing the IND to be transported across state lines, and thus permit for the preclinical evaluation for safety prior to approvals and commercial development.

There are three types of IND:

The IND application must contain information in three broad areas:

The overall quality of an IND application is largely dependent on an understanding of the requirements and its degree of compliance with FDA guidance documents. Once the sponsor submits an IND, the sponsor must wait 30 calendar days before initiating any clinical trials. During this period, FDA has an opportunity to review the IND for safety to assure that the research subjects will not be subjected to unreasonable risk. With a former FDA lead reviewer as a member of INGENES Regulatory Consulting, we understand how to evaluate product data and plan the regulatory strategy, as well as ensure clarity, accuracy and consistency within documents to be included in the IND and NDA.

Also, we can prepare and manage the IND submission for foreign companies and act as the appointed U.S. Agent.

INGENES integrated regulatory consulting services are designed to enhance the quality, organization and completeness of your submission to FDA for NDA applications. Our regulatory consultants are guided by four key principles at every stage:

A 505(b)(1) application is an application that contains full reports of investigations of safety and effectiveness. In such an application, the studies submitted for approval were conducted by, or for the applicant, or the applicant has obtained a right of reference or use for the investigations.

A 505(b)(2) application is an application that contains full reports of investigations of safety and effectiveness but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.

The applicant and FDA will rely on previous findings of safety and effectiveness that led to approval of an NDA or on data not developed by the applicant such as published literature. 505(b)(2) applications are submitted under section 505(b) of the Act and are therefore subject to the same statutory provisions that govern 505(b)(1) applications in that they require, among other things, “full reports” of safety and effectiveness.

INGENES distinctive process for 505(b)(2) submissions is one of the most efficient and effective in the industry. The average time-to-market for our clients who use this approval route is two to two-and-one-half years from the initiation of the clinical program. INGENES proven success with this type of application results from our consultant’s detailed knowledge of FDA filing requirements, good understanding of FDA review process, and use of established and well-accepted techniques, methodologies, and design of well-focused clinical studies.

An abbreviated new drug application (ANDA) is described under section 505(j) of the Act as an application that contains information to show that the proposed product is identical in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics and intended use, among other things, to a previously approved application (the reference listed drug (RLD)).

ANDAs do not contain clinical studies as required in NDAs but are required to contain information establishing bioequivalence to the RLD. In general, the bioequivalence determination allows the ANDA to rely on the agency’s finding of safety and efficacy for the RLD.

INGENES strategic approach to successful ANDA submissions focuses on gathering the appropriate ANDA information to ensure that the submission is complete in every respect, contains the right clinical study data, meets the regulatory requirement and reviewer expectations and avoids most commonly found deficiencies for quick review and faster product approval. In order to accomplish this, INGENES regulatory consultants rely on our years of experience and expertise to power bioequivalence (BE) studies appropriately and minimize study failures. This competency in clinical study design is invaluable for ANDAs that require clinical endpoint studies.

A supplement is a request to the FDA to approve a change in a human drug application which has been previously approved. Each indication or claim is considered a separate change for which a separate supplement should be submitted. This policy allows FDA to approve each indication or claim when it is ready for approval rather than delaying approval until the last of a group of indications or claims is ready to be approved.

INGENES comprehensive audits of bioequivalence studies and bioanalytical analyses assure the accuracy of data submissions to the FDA and help expedite the drug approval and market launch. When sponsors of pending or approved abbreviated new drug applications(s) (ANDAs) encounter FDA challenges to their studies, they turn to INGENES for professional review and validation of findings. INGENES meets or exceeds all FDA criteria for "audits conducted by a qualified independent expert." INGENES panel of scientific and regulatory experts provides impeccable audits that meet the highest professional and FDA scrutiny.

During Phase IV, INGENES Consultants closely work with you to help increase new drug marketability. Drawing on our relationships with seasoned marketing experts in the pharmaceutical industry, we have built a solid, highly customized strategy that incorporates regulatory and marketing objectives, along with a well-defined integrated action plan to maximize the drug product's potential. From strategic product selection, branding through carefully planned project management and implementation, INGENES can help drive your product development and sales.

Some of INGENES Phase IV activities, strategy and marketing tactics may include, but are not limited to:

Ten years after issuing proposed rules to amend and update regulations regarding establishment registration and drug listing, FDA published the final rule on August 31, 2016. The amendments update and clarify existing regulations and implement most of those proposed in 2006, and which were subsequently mandated by legislative changes to the Food, Drug and Cosmetic Act (FD&C Act), particularly those requiring electronic submissions. The effective date for updated regulations is November 29, 2016.

Here are some of the key changes and clarifications:

Definitions

Establishment Registration

INGENES regulatory consultant can help you get your Company’s Establishment Registration with the FDA.

There were two major changes proposed in 2006 that were NOT incorporated into the final rule:

INGENES regulatory consultant can help you get your Company’s NDCs and Drugs Listing with the FDA.

OTC Drug Establishment Registration & Labeling Requirements

Domestic and foreign establishments that manufacture, repack, or re-label OTC drug products or import or offer for import OTC drug products to the United States require FDA drug establishment registration, and renew the registration annually; FDA drug establishment registration information should be submitted electronically using SPL files with coded data fields. US FDA encourages electronic registration, even though you can submit registration in paper format if a waiver is granted. A Private Label Distributor (PLD) does not require US FDA drug registration. A contract sterilizer and Contract Testing Laboratory (dosage forms & active ingredient release) require US FDA registration but not listing. A foreign drug manufacturer also requires US FDA registration and listing, if drug from the manufacturer is marketing in the USA.

US FDA is not pre-approving OTC Drug Labels marketed under OTC Monograph, but US FDA regulates all OTC Drug labeling like immediate container, outer package, and package insert etc. ., The required information includes Drug Facts labeling and Principle Display Panel labeling. The regulations help to Standardize the content and format of OTC Drug labeling. The registrant may upload the OTC drug labeling at the time of drug listing in SPL file format.

To obtain global marketing approval for any pharmaceutical product (whether intended for animal/human use) one of the key documents required is a Certificate of Pharmaceutical Product (CPP), which has been recommended by the World Health Organization (WHO).

It is a special type of certificate which forms parts of the marketing authorization application and enables a given pharmaceutical product to be registered and marketed in the exporting country of interest. It is the importing country who requires the CPP for the pharmaceutical product. Different strengths of pharmaceutical products require separate CPPs.

A CPP demonstrates to Regulatory Authorities in the exporting country in question that the imported medicine is of the appropriate standard of quality, safe and effective to allow marketing in their market, having undergone rigorous testing and examination. The certificate also demonstrates that the product follows the correct guidelines and procedures of Good Manufacturing Practice (GMP), increasing the level of safety and indeed quality of the product.

To obtain a CPP, a request is made by the Marketing Authorization Holder (MAH) to the exporting country’s health authority. An authorized person issues the CPP and returns it to the MAH. Other documents required to obtain a CPP include; an Application for Export Certificate form, evidence of a GMP certificate (if applicable), Manufacturing License and the last approved SPC (Summary of Product Characteristics).

To obtain a CPP, a request is made by the Marketing Authorization Holder (MAH) to the exporting country’s health authority. An authorized person issues the CPP and returns it to the MAH. Other documents required to obtain a CPP include; an Application for Export Certificate form, evidence of a GMP certificate (if applicable), Manufacturing License and the last approved SPC (Summary of Product Characteristics).

An Active Pharmaceutical Ingredients or API is the ingredient in a finished drug that has the intended therapeutic effect. FDA regulates APIs as drugs because they are drug components. FDA also regulates inactive drug ingredients, but with far less focus or stringency.

FDA monitors APIs to ensure they meet the quality and purity characteristics that they purport, or are represented, to possess. When a chemical is classified as an API, it is subject to FDA's good manufacturing practices (GMP) regulations.

FDA has taken the position currently that the FDCA and FDA regulations require the conclusion that all APIs are necessarily misbranded because they cannot meet the statutory and regulatory requirement to bear adequate directions for use. No one uses APIs in the form in which they are manufactured and distributed for further processing. However, FDA has established drug labeling exemptions for APIs as long as the drug ingredient is used for certain specific functions (clinical trials under a valid Investigational New Drug (IND) application, for further manufacturing or processing into an FDA approved drug, for pharmacy compounding, for chemical testing, research and analysis, and for law enforcement or training and teaching purposes).

When an imported API arrives in the U.S., FDA follows certain import procedures designed to ensure that the API was manufactured by a drug facility that is in compliance with FDA drug establishment registration regulations and is an appropriate source for the API. FDA ensures that the drug is listed with FDA and that an applicable drug labeling exemption exists. These procedures can cause delays in active pharmaceutical ingredient importation; however, many foreign drug manufacturers import APIs into the U.S. every day.

Ingenes regulatory consultants are very familiar with the FDA's API importation procedures, the drug labeling, drug facility registration and drug listing regulations, and the application of the FDA's drug labeling exemptions. As a result, Ingenes regularly helps all types and sizes of drug manufacturers, drug importers and drug distributors and compounding pharmacies successfully import APIs into the U.S.

Failing to comply with the FDA regulations related to API manufacturing, API labeling and importing APIs can result in FDA import detentions, FDA Import Alerts, and FDA import refusals. In many cases, FDA detains imported API shipments improperly. This happens because the international drug manufacturing industry has become so complex that FDA registration, FDA listing and FDA approval systems are not able to adequately account for the many companies that may be involved in bringing a drug to market. Ingenes often is called upon to obtain FDA release of a detained imported API shipment. Ingenes is able to find a way for your API importation or API distribution in a manner that reduces the risk that FDA will significantly intervene in the API importation.

Ingenes will make certain that our importing clients understand the importation process and assist our clients in identifying appropriate actions and responses. It is important for your company to know and follow the laws, regulations, and procedures when importing products into the United States.