Pharmaceutical Projects: Walking along the Risk Management Line

*Jordi Botet*

### **Abstract**

We manage risk so commonly (and unconsciously) in our everyday life that we tend to undervalue it. Risk management was officially introduced in the pharmaceutical world by the ICH guideline Q9 in 2005. Since then, it has been intensively used and, not infrequently, misused. Practice shows that risk assessment tools are often seen as an end in themselves, while such important things as brainstorming on the matter and getting to know the problem are underestimated. A pharmaceutical project provides a very good example of this: risk management is critical, but as there are many unknown factors, it has to be performed in a way that what really counts is understanding the problems we face. A pharmaceutical project has at least two actors, a pharmaceutical firm and an engineering company, possessing different backgrounds, and this often leads to different approaches. This may explain why risk management is not used as much as it should in pharmaceutical projects. Thus, this chapter considers a pharmaceutical project from the point of view of risk management.

**Keywords:** quality, pharmaceutical laboratory, engineering company, risk assessment tool, pharmaceutical quality system (PQS), life cycle, risk ranking and filtering (RRF), primary hazard analysis (PHA), biological agent

#### **1. Introduction**

Quality is not a matter of discussion. Quality is necessary for any manufactured product. Failures mean losses in terms of money, logistics, and prestige, and no industry can withstand these damages. Pharmaceutical products share this situation, but, besides, their lack of quality turns out to be a public health problem. This is why the authorities require that medicines meet their specifications and manufacturers have the responsibility of exclusively commercializing products possessing their purported quality.

The production of medicines is in fact composed of two different types of manufacture. Firstly, there are facilities that produce the ingredients, or active pharmaceutical ingredients (APIs), used in the preparation of the medicines. Secondly, we have those facilities, which combine the ingredients to obtain pharmaceutical forms. These latter are packed to get what we know as a drug, medicine, or pharmaceutical. This chapter focuses on this second type of manufacture, although we consider biotechnology too (in spite of producing substances, which are used as ingredients).

## **2. How to ensure quality**

Taking for granted that medicines should always meet their specifications, we should find a reliable method for ensuring this. Unfortunately, guaranteeing quality is not an easy task, and this explains why over time different strategies have been applied.

The oldest one, which we might term as "analytical quality," proposed the analysis of the finished products as the tool for determining their appropriateness. This approach has many flaws, just to mention one, the quality problem is just detected when the product is already finished (and this makes corrective measures very difficult).

Then, in the middle of the twentieth century, "manufactured quality" was introduced. This new methodology, which led to the publication of the well-known GMP (good manufacturing practices), is based on the assumption that quality should be considered as another ingredient of the product (this was termed as "built-in quality").

More recently, already in the twenty-first century, the International Council for Harmonization (ICH) has extended this latter approach to the development stages of the product in order to attain a complete control of its life cycle. The logic underlying this method is very simple. How can you manufacture a quality that you have not designed previously? This is why we came to the present situation, which considers that quality is something that you should design (quality by design), construct (built-in quality), and supervise (process and product monitoring). In order to attain these goals, it is necessary to define and implement a policy of quality, which requires the establishment of a quality system. Although different systems are possible, in 2008, the ICH proposed a pharmaceutical quality system (PQS), specially developed for the pharmaceutical industry [1].

Even though the PQS focuses on pharmaceuticals, it is evident that if we are bound to produce quality products, the unit where we manufacture them should share this same approach for quality and here, the PQS provides very useful hints regarding the quality of pharmaceutical projects.

#### **3. About the pharmaceutical project**

A pharmaceutical project can be defined as a temporary effort undertaken with the aim of creating facilities that allow manufacturing medicines with the required quality and assurance. This effort is usually a quite difficult one, because it has to be carried out by different partners, which should work together, even if pertaining to different technical areas.

The partners who take part in a project belong normally to two groupings. On one side, the "client" (that is, the pharmaceutical laboratory or, maybe, laboratories) desires to possess new manufacturing premises or modify old existing ones. On the other side, the "supplier" usually consists of an engineering company that in fact coordinates different suppliers, extending from the providers of construction materials and associated services to the sellers of pharmaceutical equipment. These two parts, which to simplify matters we are going to name from now on as "laboratory" and "engineering," are usually sharply asymmetric. The laboratory in these matters, generally speaking, has a much more limited experience than the engineering, whereas the knowledge regarding pharmaceutical norms is often less developed in the engineering. The amount and importance of these differences can vary a lot, but here we have a possible source of problems that should not be overlooked and that makes very advisable tight control on a project.

**151**

**Figure 1.**

*Structure of the PQS (ICH Q10).*

*Pharmaceutical Projects: Walking along the Risk Management Line*

pharmaceutical project. Let us analyze this (**Figure 1**).

quality manual should address the following topics:

of GMP to a development laboratory).

chief leading it.

**4. Structure of a pharmaceutical quality system (PQS)**

The paradigm of quality described by the ICH guidelines, Q8 to Q12 [1, 2–5], should also be applied to pharmaceutical projects, but taking into account the existing differences between manufacturing and managing a project. This is why not all the elements of a quality system devised for products can be applied into a

The development and implementation of a PQS is the result of the definition of a quality policy by a laboratory. In order to put this policy into practice, the company writes a quality manual and associated documents that develop it in more detail. A

1.The PQS is devised to ensure the application of GMP by the laboratory. As shown in **Figure 1**, the PQS covers the whole life cycle of a medicine, excluding the stage of development (this is the consequence of an old tradition of working in development centers and of the difficulty of applying the strict controls

2.Management responsibilities should be clearly stated. Practice shows that this is very important. As in old battles, the army can only win the war if there is a (good)

3.ICH Q10 describes two capacitors, intended to help in the task of reaching the objectives. The first one is risk management and we will discuss it in detail further on, as the main topic of this chapter. The second one is knowledge management and its intent is fighting the very pernicious practice that rules in more than one company: that is, people who get some knowledge on products

*DOI: http://dx.doi.org/10.5772/intechopen.82601*

*Perspectives on Risk, Assessment and Management Paradigms*

specially developed for the pharmaceutical industry [1].

regarding the quality of pharmaceutical projects.

**3. About the pharmaceutical project**

makes very advisable tight control on a project.

different technical areas.

Taking for granted that medicines should always meet their specifications, we should find a reliable method for ensuring this. Unfortunately, guaranteeing quality is not an easy task, and this explains why over time different strategies have

The oldest one, which we might term as "analytical quality," proposed the analysis of the finished products as the tool for determining their appropriateness. This approach has many flaws, just to mention one, the quality problem is just detected when the product is already finished (and this makes corrective measures

Then, in the middle of the twentieth century, "manufactured quality" was introduced. This new methodology, which led to the publication of the well-known GMP (good manufacturing practices), is based on the assumption that quality should be considered as another ingredient of the product (this was termed as

More recently, already in the twenty-first century, the International Council for Harmonization (ICH) has extended this latter approach to the development stages of the product in order to attain a complete control of its life cycle. The logic underlying this method is very simple. How can you manufacture a quality that you have not designed previously? This is why we came to the present situation, which considers that quality is something that you should design (quality by design), construct (built-in quality), and supervise (process and product monitoring). In order to attain these goals, it is necessary to define and implement a policy of quality, which requires the establishment of a quality system. Although different systems are possible, in 2008, the ICH proposed a pharmaceutical quality system (PQS),

Even though the PQS focuses on pharmaceuticals, it is evident that if we are bound to produce quality products, the unit where we manufacture them should share this same approach for quality and here, the PQS provides very useful hints

A pharmaceutical project can be defined as a temporary effort undertaken with the aim of creating facilities that allow manufacturing medicines with the required quality and assurance. This effort is usually a quite difficult one, because it has to be carried out by different partners, which should work together, even if pertaining to

The partners who take part in a project belong normally to two groupings. On one side, the "client" (that is, the pharmaceutical laboratory or, maybe, laboratories) desires to possess new manufacturing premises or modify old existing ones. On the other side, the "supplier" usually consists of an engineering company that in fact coordinates different suppliers, extending from the providers of construction materials and associated services to the sellers of pharmaceutical equipment. These two parts, which to simplify matters we are going to name from now on as "laboratory" and "engineering," are usually sharply asymmetric. The laboratory in these matters, generally speaking, has a much more limited experience than the engineering, whereas the knowledge regarding pharmaceutical norms is often less developed in the engineering. The amount and importance of these differences can vary a lot, but here we have a possible source of problems that should not be overlooked and that

**2. How to ensure quality**

been applied.

very difficult).

"built-in quality").

**150**
