Outsourced activities and purchased materials
As demonstrated in sections 1.7(d) and 2.7 of the final Q10 guideline, the ICH Q10 Expert Working Group took into account
the fact that the pharmaceutical world has changed and there's a lot more outsourcing of activities for any pharmaceutical
company than in years past. Whether we're talking about the largest multinational or the smallest start-up, certain aspects
of companies' operations and PQS are given to others to undertake. The management of those activities is very important from
a quality perspective and from a business perspective.
The same amount of due diligence that goes into, for example, the financial arrangements in developing contracts between the
parties regarding outsourced activities should also be put forth toward the quality aspects of those contracts. This is really
what's new in the final version of the Q10 guideline versus earlier drafts.
According to section 1.7(d), "The pharmaceutical quality system should include appropriate processes, resources, and responsibilities
to provide assurance of the quality of outsourced activities and purchased materials as described in section 2.7." Outsourced
activities, according to Q10, include "activities conducted by a contract acceptor under a written agreement with a contract
Although the definition of "outsourced activities" is broad, the intent is clear. Companies should have a written agreement
between the firm that's ultimately responsible for the pharmaceutical and the firm that's going to do the work for that pharmaceutical
Section 2.7 also addresses purchased materials. A PQS therefore involves active pharmaceutical ingredients as well as inactive
ingredients and components, or in some cases, pharmaceutical intermediates that could be purchased by a particular pharmaceutical
A key concern in this context is management responsibility of the PQS. It must be very clear in written quality agreements
or contracts which party is responsible for certain activities. It also should be clear that it's the firm that is outsourcing
these operations that is ultimately responsible for the product. Companies cannot point to the provider of an outsourced activity
and say it's their responsibility if there's a problem with a product.
These types of outsourced activities, in my view, do not just apply to the commercial realm but also to research and development
(R&D) activities (see next section). In a properly designed PQS, companies should account for outsourced activities throughout
the entire product's life cycle.
Quality systems for R&D
As previously discussed, it's important not to force commercial requirements on development, but industry definitely needs
a PQS in the development arena. Because ICH Q10 is a guideline and therefore voluntary, some in industry are not sure whether
they should adopt it or not. Furthermore, many are unclear how best to persuade management to implement the guideline, particularly
in the area of R&D.
In the US, the clinical supply chain is rarely inspected. In the European Union, the situation is different because investigational
drug inspections are a legal requirement. Nevertheless, all reputable companies recognize that there is both a legal and ethical
requirement to enforce GMP standards on any product intended for human use. Life-cycle management covers early research and
discovery, proof of concept, and preclinical studies—none of which are covered by GMPs. These early phases need some kind
quality system because they are feed items: they provide data and a solid basis for Phase I, II, and III as well as product
This is where Q10 comes into play—the elements of Q10 can be applied in an appropriate, proportionate manner to each life-cycle
stage (see Figure 2). If one looks at legacy products with regard to quality systems, they are only looking at a small part
of the product's life cycle. From discovery through commercialization, the average time for an innovative product is about
15 years. That leaves around 7–15 years of commercial life at most for a novel product. If a company wants a good return on
investment, it needs to invest in a quality system that is appropriate in the earliest stages in order to have rapid approval
and smooth production.
Figure 2: The various stages of a productlife-cycle management, including the introduction of a legacy product change.
Approximately 50% of a product's life cycle is spent in the R&D stage. Can we still argue that because regulators don't require
a formal quality system (prior to human use of products), we are wasting company resources and stifling innovation if we implement
any kind of quality system in our company? I don't think so.
With legacy products, Q10 is needed primarily for change management (see next section). Industry has been dealing with change
management for years and they're pretty good at it. But if we look at Q10 in terms of R&D, then change is inherent to the
process. We can use risk-assessment tools to mitigate potential harm to patients. We can adopt design-of-experiment tools
to accelerate process understanding and to develop control strategies.
In cases where we make changes to new products, where a PQS is involved in early R&D, we're talking about a kind of "light
quality system," similar to diet products if you will. It shouldn't be something burdensome. The quality system should be
different to the commercial system, but there are issues that need to be addressed.
For example, there are many small start-up companies that have never come into contact with GMPs and don't know what a quality
system is. When they go to an outsourcing company, they don't know what to ask for or how to define their requirements clearly
enough to get what they're looking for (see a suggested checklist at
http://pharmtech.com/ for auditing a quality system within a contract relationship). They need a quality system, especially when it comes to transferring
data into knowledge and then transferring that knowledge to stakeholders.