The importance of a toxicology study in the conceptual phase

Generally, in pharmaceutical projects and in the pharmaceutical industry, more importance is given to compliance with cGMP than to the risk caused by the toxicity of the drugs that are expected to be manufactured in the facility.

In this sector we have to comply with standards associated with GMPs and the pharmaceutical form to be manufactured (oral solids, liquids, semisolid, sterile …). In addition, we must study and define a series of issues associated with GMP compliance, such as the flow of materials and people, classification of zones, qualification of facilities and equipment…. Pharmaceutical laboratories have to go through a regulatory process in order to approve the facility, being periodically inspected to see the degree of GMP compliance.

On the other hand, when establishing in a pharmaceutical project what is the toxicological risk of the active principles that are expected to be manipulated in the plant, we find a lack of definition. Even when it is a key requirement in the first phases of the design of a pharmaceutical installation.

The causes of this ignorance can be several:

• The type of products that the plant wants to manufacture in the future is unknown. In the case of CMOs, it is critical to leave the plant ready to cover a range of products as wide as possible.
• The applicable regulations are unknown. In Spain we have some NTP (1104 and 1105) of the National Institute of Safety, Health and Well-being at Work (INSSBT) that are basic tools in order to define what are the technical and organizational measures to comply with depending on the risk of the products .
• Unlike the GMPs, there is no inspection by a public body that has to periodically certify that adequate measures are in place to protect workers.
• The health and safety department does not have the same power as other departments. This department is sometimes relegated to just a testimonial presence.

It’s important to put attention on:

• The number of products with high toxicological potency is increasing and they are especially attractive for third-party manufacturing.
• A project does not become substantially more expensive if the type of products expected to be manufactured in the future is taken into account from the outset. You can define changing rooms, material accesses, locks, HVAC compartmentalisation, access control … and leave the plant ready to be able to manufacture products with a specific toxicological risk. What makes it more expensive and in many cases it is very difficult to do is, once the plant is finished, adapt to comply with the technical measures associated with higher risk products (which is what happens in many cases).
• The technical measures have to be perfectly defined for the type of products that are expected to be manufactured and there are a series of responsibilities of the management as indicated by Law 31/1995, of November 8, on the Prevention of Occupational Risks. Article 42. Responsibilities and their compatibility.

Non-compliance by employers of their obligations in terms of prevention of occupational risks will give rise to administrative responsibilities, as well as, where appropriate, criminal and civil liability for damages that may arise from said non-compliance.

Ultimately, when a pharmaceutical project starts, it is as necessary to have a facility that complies with GMP requirements, as that complies with the technical measures associated with the toxicological risk of the products that are expected to be manufactured in the future. For this reason, a toxicology study in the definition phase can become essential to avoid risks that translate into enormous problems in the future.

If you are interested in learning more about product toxicology and how we can help you, contact us: klinea@klinea.es