The Registration Dossier Discloses Manufacturing Technology. The EAEU Master File Protects Know-How.
The registration dossier for a medicinal product requires a detailed description of the synthesis of the active substance, equipment parameters, and process validation data. An active pharmaceutical ingredient (API) manufacturer is obligated to disclose this information for the dossier to be accepted for regulatory evaluation. The Marketing Authorization Holder (MAH) is responsible for product quality, which means it must understand what the product is made of and how it is manufactured.
Both requirements clash every time an API manufacturer enters into a contract with a new partner. A single regulatory mechanism balances these competing interests without compromising either quality or technology: the Master File. Under this mechanism, one portion of the data is shared with the MAH, while the closed portion remains protected and is submitted directly to the competent authority.
A mistake in this division can cost a company years of R&D. The following analysis examines how this protection operates under EAEU and Russian law, where vulnerabilities arise, and what steps are necessary to maintain control over proprietary technology.
Why a Patent Is Not Suitable for Protecting Manufacturing Technology
A patent grants a monopoly over an invention in exchange for the complete disclosure of its essence in a public register. For an active substance, this works: the chemical formula and the method of production become public, and in return the manufacturer receives an exclusive right for 20 years. However, most manufacturing details (temperature profiles, reagent addition sequences, purification parameters) do not make it into the patent application and remain unpatented.
A trade secret (know-how) functions differently. Article 1465 of the Civil Code of the Russian Federation defines a trade secret (know-how) as information of any nature, including manufacturing, technical, and organizational information, regarding the results of intellectual activity and methods of conducting professional activities. There are three statutory criteria for protection: the information possesses actual or potential commercial value because it is unknown to third parties; third parties do not have lawful free access to it; and the rights holder takes reasonable measures to maintain its confidentiality, including implementing a commercial secret regime.
Under Article 1467 of the Civil Code, the term of an exclusive right to a trade secret is not tied to a calendar date. The right exists as long as confidentiality is preserved. The moment confidentiality is lost, the exclusive right terminates immediately for all holders, including those who acquired the information lawfully. Know-how is well suited for technologies that cannot be readily reverse-engineered by analyzing the finished product. The weakness mirrors the strength: a single leak destroys the protection immediately and permanently.
| Parameter | Patent | Trade Secret (Know-How) |
|---|---|---|
| Legal basis | Civil Code, Part Four, Chapter 72 | Civil Code, Part Four, Chapter 75 |
| Duration of protection | Limited, typically 20 years | Valid as long as confidentiality is maintained |
| State registration | Mandatory | Not required |
| Disclosure | Full disclosure in a public registry | Strictly limited circle of persons |
| Risk of independent creation | Protects even against parallel independent development | Does not protect if the same information is obtained independently and in good faith |
The independent, parallel development of a technology by a competitor does not infringe anyone’s know-how rights. Paragraph 2 of Article 1466 of the Civil Code expressly grants such a competitor an independent exclusive right to that same secret. A patent protects against this risk; know-how does not.
The choice between the two regimes depends on whether the solution can be reverse-engineered. The molecular composition, dosage form, and dosing method can almost always be deduced by analyzing the finished drug product, so a patent provides genuine protection for these elements. Reactor temperature profiles, catalyst addition sequences, or intermediate purification protocols, by contrast, are not discernible in the finished drug, and a patent application for them is more likely to expose the technology to competitors than to protect it. For such parameters, a commercial secret regime managed through a Master File works better than a public patent application.
The Active Substance Master File Splits Technology into Two Parts
The Active Substance Master File (ASMF) procedure is governed by the Rules of Registration and Examination of Medicinal Products for Medical Use, approved by Decision of the EEC Council No. 78 dated 3 November 2016 (hereinafter, Decision No. 78). It resolves the conflict between the API manufacturer and the MAH of the finished drug: the MAH is obligated to control raw material quality, but has no obligation to know the technology behind its production.
This is achieved by splitting the ASMF into an Applicant’s Part (open part) and a Restricted Part (closed part). The MAH receives the Applicant’s Part and incorporates it into its own registration dossier. It contains general properties of the active substance, specifications, control methods, and stability data. The Restricted Part stays with the API manufacturer and is submitted directly to the competent authority of the Member State together with a Letter of Access, which authorizes the assessor to rely on this data when evaluating the specific medicinal product.
| ASMF Section | Who Gets Access | Typical Content |
|---|---|---|
| Applicant’s Part | MAH, regulatory assessor | Specifications, control methods, stability data, impurity profile |
| Restricted Part | Competent authority only | Detailed synthesis route, equipment parameters, validation of critical steps |
| Letter of Access | Competent authority | Authorization to rely on the Restricted Part when evaluating the specific product |
The MAH does not gain access to the Restricted Part either at dossier submission or during subsequent inspections. It sees only the outcome: the assessor’s confirmation that the substance meets specification. The synthesis route, catalysts, and process intermediates remain outside the MAH’s view, and therefore outside the view of its own contract manufacturers and subcontractors.
The obligation to keep this information confidential does not rest on the API manufacturer alone. Paragraph 11 of Decision No. 78 directly imposes on the competent authorities and expert organizations of the Member States a duty to ensure the confidentiality of registration dossier information, including the Restricted Part of the ASMF. Once submitted, the technology is protected not only by the contract with the MAH, but also by a separate statutory duty of the regulator, one that exists independently of what the contracting parties themselves agree.
A similar architecture is used by major regulators outside the Union. In the European Union, the Active Substance Master File procedure splits the dossier into an Applicant’s Part and a Restricted Part, and the regulator’s access to the closed part is unlocked by a Letter of Access from the file holder. In the United States, the Food and Drug Administration accepts Drug Master Files under several types: Type II for the substance, Type III for packaging materials, Type IV for excipients. Type I, which described the manufacturing site, was closed to new submissions by the FDA back in 2000.
Health Canada uses its own Master File with a similar split into an Applicant Part and a Restricted Part, and a separate Letter of Access for each reference. The logic is the same everywhere: only the regulator sees the closed data, while the substance purchaser sees the open data.
The Pharmacovigilance Master File Protects a Different Category of Information
The Pharmacovigilance System Master File (PSMF) is built around a different subject of protection: the internal organization of the drug safety monitoring system. Its structure is set out in Decision of the EEC Council No. 87 dated 3 November 2016, «On the Approval of the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union» (hereinafter, Decision No. 87). It requires the MAH to describe in detail the structure of the system, the distribution of responsibilities, and the procedures for collecting adverse reaction data.
The PSMF contains a great deal of open procedural information. Its practical value for a competitor lies in a different layer: signal detection methods, causality assessment algorithms, the architecture of the company’s own database, and internal performance indicators of the system. These elements distinguish one MAH from another and constitute know-how within the meaning of Article 1465 of the Civil Code, regardless of the fact that the file itself is submitted to the regulator under a mandatory requirement.
The rules under Decision No. 87 require the master file to be kept at the place where the main pharmacovigilance activity is carried out within the Union or, if that place cannot be determined, at the location of the qualified person for pharmacovigilance (QPPV). An inspector may arrive without notice, and at that moment the complete file must be at hand. Together, these two requirements mean a company cannot keep its PSMF outside EAEU territory while also expecting it to be immediately available for inspection.
For the Russian market, the requirement to hold such a file is also fixed at the level of national law. Article 9 of Federal Law No. 61-FZ dated 12 April 2010, «On the Circulation of Medicines,» classifies the pharmacovigilance system master file and the risk management plan among the information that the registering authority transmits, upon request, to the supervisory authority as part of interagency cooperation. Part 2.1 of this article expressly permits such a transfer even if the information constitutes a commercial secret. For the compliance function, this is a distinct risk: the company’s confidential data moves lawfully between two state authorities without its involvement in the process, and the MAH cannot control this channel, only account for it in its risk assessment.
Holding a PSMF adds another layer of requirements. The file is linked to data on pharmacovigilance specialists and, indirectly, to patient data, so protecting it requires simultaneous compliance with the commercial secret regime and with Federal Law No. 152-FZ dated 27 July 2006, «On Personal Data.» Shared use of a pharmacovigilance system by several companies, for example under a licensing agreement for a product, raises the risk: one party’s file can expose the other’s operational details. Separate file modules for each MAH and a detailed Pharmacovigilance Agreement (PVA) that clearly separates rights to different parts of the information help here.
The CMO Agreement Determines the Ownership of Process Improvements
Transferring manufacturing technology to a contract manufacturing organization (CMO) is the point of greatest vulnerability for know-how. At this stage the trade secret leaves the company and reaches a third party, while most manufacturing details have no patent protection.
The Civil Code distinguishes two contractual mechanisms. Assignment of the exclusive right under Article 1468 transfers the trade secret in full and makes the CMO the new rights holder; the former holder, after the deal, remains obligated to keep it confidential until the exclusive right expires. For a technology transfer to a facility that manufactures the drug on the developer’s order, this model is almost never suitable: the developer wants to keep control of the technology, not hand it over.
Transfer practice fits Article 1469 of the Civil Code, the license agreement for the use of a trade secret. Under such an agreement, the licensor grants the licensee the right to use the technology within the limits set by the contract, not ownership of it. Paragraph 3 of Article 1469 places a confidentiality obligation on both parties: the licensor must keep the secret for the entire term of the agreement, and the licensee, once it has gained access to the information, must keep it confidential until the exclusive right itself expires, meaning even after the collaboration ends.
A contract with a CMO is worth supplementing with conditions the Civil Code does not spell out, but which decide the outcome of a dispute when the relationship ends:
a ban on using the technology for any products other than the licensor’s;
an obligation to return or destroy the documentation, including electronic copies and working records, once the collaboration ends;
the licensor’s right to an unscheduled audit of the partner’s information security;
a procedure for notifying both parties of any incident that threatens confidentiality.
A separate risk involves the improvements a CMO makes to the process while mastering the product. Article 1471 of the Civil Code sets a default rule: if a trade secret is obtained while performing a work contract or R&D, design, or process-engineering work, the exclusive right to it belongs to the contractor, unless the contract provides otherwise. For a pharmaceutical company, this means that without an explicit contractual clause, a process improvement found at a CMO legally belongs to the CMO, not to the client.
A similar question arises inside the company itself. Article 1470 of the Civil Code vests the exclusive right to a service-related trade secret in the employer, if the employee created it in connection with their job duties or a specific assignment. An employee who learns such a secret through their work is obligated to keep it confidential until the exclusive right expires. The rule applies automatically, but relying on it alone is risky: without a clear job description and an order marking the start of a specific development project, it is hard to prove that a synthesis method a departing process chemist considers their own personal experience actually belongs to the employer as a service-related trade secret.
The same split-access logic applies to primary packaging materials. Suppliers of vials, closures, and blister film often protect their polymer composition and surface-treatment parameters through their own master file, giving the pharmaceutical company only a Letter of Access to that data for its registration dossier. In the FDA’s classification these files fall under Type III. The closed data on polymers and extrusion temperature profiles are available to the assessor, but not to the buyer of the packaging.
The move to the electronic Common Technical Document format adds a digital dimension to these same risks. The closed part of a master file, once exported from an electronic document management system, can be copied without loss of quality and distributed instantly. Section-level access rights, user activity logs, and limits on bulk export reduce this risk. They do not remove it entirely: a trained and motivated insider with legitimate access remains a source of leaks that no single technical measure blocks on its own.
What to Do
Audit every technology the company currently protects as know-how. Separate what is easy to reverse-engineer from the finished product or find in open sources from what genuinely holds commercial value because it is unknown to third parties.
Put a commercial secret regime in place under Federal Law No. 98-FZ dated 29 July 2004, «On Commercial Secrets.» Define the list of protected information, the access procedure, a record of who has been given access, and the «Commercial Secret» stamp on carriers and in document details.
Check every license and contract manufacturing agreement covering a technology transfer against Article 1469 and Article 1471 of the Civil Code. Make sure the contract states directly who owns the rights to process improvements found at the CMO, and that it provides for returning or destroying documentation once the collaboration ends
Agree with your API and packaging suppliers on the procedure for filing and updating their master files. Ask for confirmation that the closed part has been filed with the regulator directly, and that the Letter of Access is current for every product that uses this substance or this packaging.
Restrict internal access to the closed parts of master files and PSMFs through a document management system with metadata-level access rights. Audit access rights after R&D staff who had access to the closed files leave the company, and after projects with CMOs close out.
A master file does not remove the risk of the technology being disclosed. It simply moves the point of control from a commercial partner to a regulator that the law already requires to keep secrets. The split between the open and closed parts works only where a company has already decided what information makes up its know-how, and has backed that decision with a contract, a commercial secret regime, and a technical limit on access. Without that groundwork, even a flawlessly filed master file will not save a technology from a leak through the weak link. In practice, that weak link is almost always the company’s own contract partner: closest to the technology, and least bound by the regulator’s obligations.
Regulatory Framework:
1. Decision of the Council of the Eurasian Economic Commission No. 87 dated 3 November 2016, «On the Approval of the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union» (as amended by Decision of the Council of the Eurasian Economic Commission No. 81 dated 19 May 2022)
2. Civil Code of the Russian Federation (Part Four), Chapter 75, Articles 1465, 1466, 1467, 1468, 1469, 1470, 1471, 1472
3. Federal Law No. 98-FZ dated 29 July 2004, «On Commercial Secrets»
4. Federal Law No. 61-FZ dated 12 April 2010, «On the Circulation of Medicines,» Article 9
5. Federal Law No. 152-FZ dated 27 July 2006, «On Personal Data»
6. Decision of the Council of the Eurasian Economic Commission No. 78 dated 3 November 2016, «On the Rules of Registration and Examination of Medicinal Products for Medical Use»