Meredith P. Vanderbilt, JD, RAC, CQA, MSE, BSE, Director of Consulting, Empirical06.04.24
How can your company turn a specialized manufacturing process or material into a continuous revenue stream without divulging confidential information to the client directly or through the 510(k), PMA, or IDE submission process? Quick answer: Device Master Files (MAF).
The PMA process requires an independent demonstration of a new device’s safety and effectiveness through the presentation of scientific, technological, and clinical data for a Class III medical device. Detailed descriptions of all processes, materials, validations, and formulations must be included in the required scientific data to be presented in a PMA, and an extensive summary of all data is made available on the PMA database.
The purpose of a 510(k) submission is to prove substantial equivalence to another device in the market, also known as a predicate device. In rare cases, the subject device is identical to the predicate device, but it is more common the two devices have the same intended use with differing technological characteristics. According to FDA’s guidance document for proving substantial equivalence, the 510(k) submission “contains information, including appropriate clinical or scientific data…that demonstrates that the device is as safe and effective as a legally marketed device,” and “does not raise different questions of safety and effectiveness than the predicate device.”
In both PMA and 510(k) submissions, material and process data are critical in the FDA’s evaluation. Both types of submissions require a complete identification of the detailed chemical formulation used in the materials of construction, especially for materials that come into contact with the patient. This is one of the important concepts for contract manufacturers who have specialized materials, manufacturing processes, surface treatments, or coatings for which the formulation or method is considered a trade secret. While the contract manufacturer cannot avoid sharing confidential information with the FDA, it is undesirable to share the same information with all clients, customers, and consultants involved in the submission process.
Although the FDA is required to maintain the confidentiality of regulatory submissions within the confines of the Freedom of Information Act (more discussion about FOIA to come) and information that is statutorily available on public databases, submissions are drafted and submitted by sponsors or applicants and their consultants. Manufacturers likely have non-disclosure agreements (NDAs) in place with their clients, and they likely have NDAs in place with their consultants and suppliers. While there is plenty of case law to support the rights of all parties to these NDA contracts, once your “secret sauce” formula has been released to your competitors, there is no pulling those trade secrets back. (You cannot unscramble that egg, as my grandmother used to say.)
The commercial value of your “secret sauce” has just disappeared. MAF usage protects the contract manufacturer from competitors acquiring from their customers the “special sauce” that makes a process or material commercially valuable.
Only you, the MAF holder, and the FDA know what is in that drawer, and no one can access that information except those with the magic FDA key. No one can request the FDA use the information in the “MAF 07021998 Gilderoy – Brackium Emendo” drawer without your written permission. The FDA cannot release any information within the “MAF 07021998 Gilderoy – Brackium Emendo” drawer. What you are envisioning is an FDA MAF.
MAFs may be submitted for various functions, according to the FDA website. These functions have been grouped by the following types:
There are no specific content requirements for an MAF but it must be substantive and contain information that may reasonably be regarded as a trade secret or confidential commercial or financial information. The submission must include a cover letter on company letterhead that is signed by a responsible official (e.g., Director of Regulatory Affairs or another manager). The letter should identify the submission as an MAF, and a contact person at the company or a designated agent should be listed. An MAF must be in the English language or accompanied by accurate English translations of any of the documents in a language other than English.
After the FDA has referred to an MAF and the client’s submission has been cleared or approved, authorization cannot be withdrawn.
MAF holders should identify information in their MAFs they consider to be trade secret or confidential commercial/financial information within the meaning of 21 CFR 20.61. MAF information already in the public domain is subject to disclosure (e.g., any published literature, catalog, or product specification sheets distributed by the MAF holder to potential customers).
Meredith P. Vanderbilt is an internationally known medical device regulatory affairs consultant unafraid to communicate directly and honestly with regulatory bodies and clients about strategies and submissions to provide compliant and high-quality devices to the market.
What Information Is Provided in FDA Submissions?
The FDA requires full access to data and technical information to evaluate a submission for clearance or approval. The Pre-Market Approval (PMA) process for Class III devices is more extensive than the Pre-Market Notification [510(k)] process for Class II devices, but both require submission of technical data.The PMA process requires an independent demonstration of a new device’s safety and effectiveness through the presentation of scientific, technological, and clinical data for a Class III medical device. Detailed descriptions of all processes, materials, validations, and formulations must be included in the required scientific data to be presented in a PMA, and an extensive summary of all data is made available on the PMA database.
The purpose of a 510(k) submission is to prove substantial equivalence to another device in the market, also known as a predicate device. In rare cases, the subject device is identical to the predicate device, but it is more common the two devices have the same intended use with differing technological characteristics. According to FDA’s guidance document for proving substantial equivalence, the 510(k) submission “contains information, including appropriate clinical or scientific data…that demonstrates that the device is as safe and effective as a legally marketed device,” and “does not raise different questions of safety and effectiveness than the predicate device.”
In both PMA and 510(k) submissions, material and process data are critical in the FDA’s evaluation. Both types of submissions require a complete identification of the detailed chemical formulation used in the materials of construction, especially for materials that come into contact with the patient. This is one of the important concepts for contract manufacturers who have specialized materials, manufacturing processes, surface treatments, or coatings for which the formulation or method is considered a trade secret. While the contract manufacturer cannot avoid sharing confidential information with the FDA, it is undesirable to share the same information with all clients, customers, and consultants involved in the submission process.
Although the FDA is required to maintain the confidentiality of regulatory submissions within the confines of the Freedom of Information Act (more discussion about FOIA to come) and information that is statutorily available on public databases, submissions are drafted and submitted by sponsors or applicants and their consultants. Manufacturers likely have non-disclosure agreements (NDAs) in place with their clients, and they likely have NDAs in place with their consultants and suppliers. While there is plenty of case law to support the rights of all parties to these NDA contracts, once your “secret sauce” formula has been released to your competitors, there is no pulling those trade secrets back. (You cannot unscramble that egg, as my grandmother used to say.)
The commercial value of your “secret sauce” has just disappeared. MAF usage protects the contract manufacturer from competitors acquiring from their customers the “special sauce” that makes a process or material commercially valuable.
What Is a Master File?
For simplicity, imagine you work for the company Gilderoy Industries, and you have a surface treatment process named Brackium Emendo that can instantly fuse bone to a metal or polymer implant in a controlled and predictable manner. Imagine a large, locked room full of vintage filing cabinets where one of the drawers is labeled “MAF 07021998 Gilderoy – Brackium Emendo”. Inside that drawer is a well-organized set of folders with all the confidential information needed for the FDA to understand how the process works and the test reports to prove its effectiveness and safety. There are chemical formulas, manufacturing techniques, animal studies, clinical trials, biocompatibility studies, mechanical tests, etc.Only you, the MAF holder, and the FDA know what is in that drawer, and no one can access that information except those with the magic FDA key. No one can request the FDA use the information in the “MAF 07021998 Gilderoy – Brackium Emendo” drawer without your written permission. The FDA cannot release any information within the “MAF 07021998 Gilderoy – Brackium Emendo” drawer. What you are envisioning is an FDA MAF.
MAFs may be submitted for various functions, according to the FDA website. These functions have been grouped by the following types:
- facilities and manufacturing procedures and controls; synthesis, formulation, purification, and specifications for chemicals, materials (e.g., an alloy, plastic, etc.), or subassemblies for a device;
- packaging materials;
- contract packaging and other manufacturing (e.g., sterilization);
- nonclinical study data; and
- clinical study data.
Master File Content and Submission Process
An MAF is submitted through the CDRH Portal in eCopy format. Receipt of all new MAF submissions will be acknowledged by letter to the MAF holder and include the FDA-assigned MAF reference number, such as the “MAF 07021998” in our example. This MAF number must be included in all amendments, authorizations, or references to the MAF in communications with the FDA. A holder can amend the MAF by submitting the amendment through the CDRH Portal and referencing the applicable MAF number.There are no specific content requirements for an MAF but it must be substantive and contain information that may reasonably be regarded as a trade secret or confidential commercial or financial information. The submission must include a cover letter on company letterhead that is signed by a responsible official (e.g., Director of Regulatory Affairs or another manager). The letter should identify the submission as an MAF, and a contact person at the company or a designated agent should be listed. An MAF must be in the English language or accompanied by accurate English translations of any of the documents in a language other than English.
Review of Master File Data
In our imagined library full of vintage filing cabinets, Madam Irma Pince is the librarian and keeper of the magic key to access the information. She is very capable of finding and protecting information, but she is not technically capable of assessing or testifying to the validity of the information found in every drawer and folder of every MAF. She does not inspect your technical documents before filing them in the “MAF 07021998 Gilderoy – Brackium Emendo” drawer. No one inspects your documents until specifically requested as part of a regulatory submission. This is an important aspect of the MAF process because it will not be reviewed or challenged by the FDA until it is referenced in a submission. This is why many MAF holders will partner with the company that will be the first authorized company to reference the MAF; Gilderoy Industries can have confidential conversations with the FDA about any concerns during the review process and amend the MAF where needed.Authorization to Reference the Master File
Information in an MAF may be incorporated by reference in a client's submissions to FDA only when authorized by the MAF holder, Gilderoy Industries. This authorization letter should be provided directly to the client on company letterhead and include instructions that: (1) the original of the authorization letter be included in the original copy of the client's submission and (2) a copy be placed in each subsequent copy of the client's submission. An authorization letter should not be sent directly to CDRH for inclusion in the MAF or the client’s submission.After the FDA has referred to an MAF and the client’s submission has been cleared or approved, authorization cannot be withdrawn.
Freedom of Information Act (FOIA)
Because Gilderoy Industries deems its process as a trade secret and the MAF process is designed to protect those secrets, it is important to note the role the FOIA plays in FDA disclosure. Under the Freedom of Information Act, information in 510(k)s, IDEs, PMAs, and other device-related submissions such as MAFs, is subject to public disclosure unless the FDA determines it to be trade secret or confidential commercial or financial information within the meaning of 21 CFR 20.61, or otherwise prohibited from public disclosure. FOIA public disclosure provisions apply whether or not the information in the 510(k), IDE, PMA, or other device-related submission was submitted by the applicant or is included by authorized reference to an MAF.MAF holders should identify information in their MAFs they consider to be trade secret or confidential commercial/financial information within the meaning of 21 CFR 20.61. MAF information already in the public domain is subject to disclosure (e.g., any published literature, catalog, or product specification sheets distributed by the MAF holder to potential customers).
Meredith P. Vanderbilt is an internationally known medical device regulatory affairs consultant unafraid to communicate directly and honestly with regulatory bodies and clients about strategies and submissions to provide compliant and high-quality devices to the market.