Drug Precursors Regulated by the European Union: 2 New Substances in Delegated Regulation (EU) 2025/1475

1. What are drug precursors regulated by the European Union?

2. What obligations must operators marketing Category 1 and 2 drug precursors in the EU comply with?

3. Which are the 2 new substances included and why?

4. What is the mission of the updated regulations?

5. Implementation of the amendments in the corresponding annexes

6. What are the implications of the amendments?

7. Entry into force and application of the amendments

8. Do you want to keep your database up to date?

The European Commission strengthens the control of drug precursors regulated by the EU through Delegated Regulation (EU) 2025/1475, adopted on 21 May 2025. The regulation amends Regulation (EC) No 273/2004, intra-Community control, and Regulation (EC) No 111/2005, trade with third countries. This measure was taken to include two key substances in the list. Below, we explain which substances have been added and everything you need to know about the amendment on drug precursors and its implications for the industry.

What are drug precursors regulated by the European Union?

Drug precursors regulated by the European Union are chemical substances that, due to their composition, can be used for illicit purposes. In other words, they can be used for the production of various types of drugs such as amphetamines, cocaine, heroin, among many others.

These substances are classified into the following categories:

• Category 1 substances: used in organic synthesis, medical research, pharmaceuticals, plastics, perfumery, soaps, or beverage flavors, among others. They are essential for the production of most drugs, which is why the strictest measures are imposed.

• Category 2 (subcategories 2A and 2B): used in dyes, perfumery, pharmaceuticals, paper, oils, fats, resins, bleaching agents, waxes, cotton, silk, etc. They are highly important in the production of drugs such as cocaine or heroin and are essential in the process of obtaining synthetic drugs.

• Category 3: widely used in industrial and household applications, for example, solvents and acids in plastics, photography, painting, preservatives, food, metals, among others. In this case, control measures are more flexible, since they are not essential in the drug production process.

• Category 4: in December 2013, this category was introduced into legislation regarding trade between the EU and third countries, covering human and veterinary medicines containing ephedrine or pseudoephedrine.

You can also read the consolidated text of the regulation on its official page. Now, let’s talk about the latest amendment that has included two new substances in the list of regulated precursors.

What obligations must operators marketing Category 1 and 2 drug precursors in the EU comply with?

Among the obligations for entities marketing drug precursors regulated by the EU in Categories 1 and 2, we highlight:

• Before they can possess or place on the market substances listed in Category 1, 2, and 2A of Annex I (Art. 3 Regulation (EC) 273/2004), they must hold a license granted by the competent authorities of the Member State in which they are established and be registered in the register of those authorities.

• Documenting commercial transactions (with some exceptions) (Art. 5 Regulation (EC) 273/2004).

• Regarding labelling, as indicated in Art. 7 of Regulation (EC) 273/2004, they must ensure that substances listed as Category 1 and 2 drug precursors in Annex I are labeled before supply. (The name appearing on the label must be the one mentioned in Annex I. They may also include their usual labels).

• Immediate notification to the competent authorities (CITCO) of any suspicious order or transaction (Art. 8 Regulation (EC) 273/2004).
  

Failure to comply with the obligations set out in these regulations, except for the exceptions reflected in them, leads to certain penalties. Therefore, it is essential to be aware of the subject and comply with the regulation.

Which are the 2 new substances included and why?

The most recently included substances in the list of drug precursors regulated by the European Union are 4-piperidone and its derivative 1-boc-4-piperidone.

These are highly relevant precursors in the manufacture of fentanyl, a powerful opioid substance, and several of its analogues. Below we explain each one:

• 4-piperidone can be transformed into other compounds such as N-phenethyl-4-piperidone (NPP), 4-anilino-N-phenethylpiperidine (ANPP), N-phenylpiperidin-4-amine (4-AP), and norfentanyl. All of these are internationally regulated by the 1988 United Nations Convention due to their use in illicit drugs.
  

• Its derivative, 1-boc-4-piperidone, is a chemically protected derivative and can be used to manufacture tert-butyl 4-anilinopiperidin-1-carboxylate (1-boc-4-AP) and subsequently norfentanyl or even be converted back into 4-piperidone.
  

It seems clear, but it is worth emphasizing that these substances act as drug precursors, i.e., as starting ingredients in the synthesis routes of fentanyl and its analogues.

Both fentanyl and its derivatives are highly potent narcotics (between 10 and 100 times more potent than heroin), and therefore, small amounts of these two precursors are sufficient to manufacture millions of doses of the final product.

What is the mission of the updated regulations?

Regulation (EC) No 273/2004 establishes surveillance measures for the trade of drug precursors within the European Union. Meanwhile, Regulation (EC) No 111/2005 regulates the trade of drug precursors between the Union and third countries.

Annex I of Regulation (EC) No 273/2004 and the Annex of Regulation (EC) No 111/2005 contain lists of scheduled substances, subject to various harmonized control and monitoring measures provided for in those Regulations.

The United Nations Commission on Narcotic Drugs, in March 2024, added the substances 4-piperidone and 1-boc-4-piperidone to Schedule I of the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (“1988 United Nations Convention”).

Therefore, to align the European framework with these changes, Delegated Regulation (EU) 2025/1475 establishes that the substances 4-piperidone and 1-boc-4-piperidone must be included in Annex I of Regulation (EC) No 273/2004 and in the Annex of Regulation (EC) No 111/2005.

Implementation of the amendments in the corresponding annexes

In Annex I of Regulation (EC) No 273/2004 and in the Annex of Regulation (EC) No 111/2005, in the Category 1 table, the following entries are added:

What are the implications of the amendments?

• Economic operators: must obtain licenses, register operations, and comply with additional controls for these Category 1 substances.

• National authorities: must update their official lists, train their staff, and coordinate inspections and sanctions.

• Public security: the central objective is to make it more difficult to illegally manufacture opioids such as fentanyl on an industrial or clandestine scale.

Entry into force and application of the amendments

The Regulation entered into force in August 2025, 22 days after its publication in the Official Journal of the EU on 25 July. The provisions introduced by the amendments became directly applicable in all Member States without the need for transposition.

Do you want to keep your database up to date?

Keeping the substance database up to date, according to current regulations, is the best way to avoid errors in chemical product management. For this purpose, it is highly advisable to use a specialized tool such as the eQgest software.

The program continuously updates the regulatory database to reflect any changes in the list of drug precursors regulated by the European Union and automates the updating of Safety Data Sheets (SDS) and other documents. The software enables proactive compliance management, adapting to your needs and those of the sector.

Contact us to learn more and discover how we can help you.