QA and supply chain

What should a QP be checking/reviewing?

cheryl-chia@xs4all.nl — Fri, 18 Nov 2022 12:10:05 GMT

How can we make the best use of the QP's knowledge and experience?

QPs are busy people. The list of QP responsibilities is growing daily and the workload of QPs is ever increasing. QPs are expected to perform to a very high level of quality, almost perfection. The public, regulatory authorities, pharmaceutical companies and patients all put their faith in QPs being the gatekeepers of pharmaceutical product quality, who take personal accountability that the product they release for distribution is safe and effective.

With that level of responsibility and expectations on their shoulders, one would imagine that the QP is superhuman. Yet a QP is a person like any other, doing the best they can. Like any other person, QPs also make mistakes, take wrong decisions and get overwhelmed with the workload, under the pressure of the enormous responsibility and all the balls they have to juggle.

How can we help our QPs and by extension, the QA teams that support the QPs, to make all that work more manageable?

Let's take batch release reviews as an example.

There are so many things to be checked in batch-related documentation, it's very easy to miss or overlook something. To help us remember what to check, we make checklists for QA and QPs. Checklists that seem to get longer and longer.

What about if we rethink the whole concept? Can we automate some or even most of these aspects that are listed in these checklists? Comparing data elements between systems or documents and checking the completion of data entry fields can surely be done by computerised systems?

What about if we critically look at all the aspects that a QP currently checks (using their checklists) and pick out only the aspects that call on the specific knowledge and experience of a QP, which cannot be quantified or written into an algorithm? For example, deliberating the impact of deviations that might indirectly impact product quality; or assessing the downstream impact of a proposed change to an analytical method of a drug substance.

At the same time, perhaps we can ask ourselves if we as QPs are sufficiently critical about all the things we have to check, review, assess, evaluate, approve, etc? I'm not saying that we should put ourselves out of a job (that's not likely to happen) but perhaps we can consider if we're using the systems available to us in the best way? Are there ways that the systems could benefit our processes, which we could make use of by changing the way we work?

Do we know our systems well enough to trust them, so that we feel comfortable about leaving out those checks and trusting the systems?

Personally, I've found it challenging to let go of my long checklists and trust the "new-fangled" computerised systems. The solution that I found was to familiarise myself with the potential and limits of the systems that I work with, getting a better understanding of how the systems are setup and tested, what the failure modes might be as well as the detection of failures if they occur, and most of all, understanding what the data sources are - the "source of truth" that influences subsequent parts of the process.

Checking less and relying more on the systems meant that I've become more involved in setting up the systems, building-in structure and system rules that make it easier for QA and QPs to rely on them, therefore allowing the QPs to focus on the aspects that rely on a QP's judgment, discretion, pragmatism and sometimes even courage. All the human factors that cannot be replicated in an algorithm to be executed by a computerised system.

The reality is that there are not enough QPs to go around. The QPs that we have are overworked and sometimes perhaps a little frustrated at the minutiae that they have to deal with. Perhaps if we rethink and redesign our QA and QP processes, with some QP creativity and pragmatism, we could make QP work more fulfilling and less routine?

QP and finished product distribution

Fri, 10 Dec 2021 16:28:22 GMT

How much involvement should a QP have in the distribution of the finished product that they have certified?

My presentation at the recent ECA QP Forum included QP oversight of the distribution of the finished medicinal product, after QP certification.

Questions were raised as to the level of involvement that a QP should have in the distribution of the finished product after QP certification. After all, Annex 16 only states that QPs should have oversight of the supply chain from active substances to finished product certification.

We didn't have enough time to dive into the details of this during the Q&A session, so I've decided to write this blog. Hopefully it will reach (some of) the QPs who wanted this point clarified.

Let's start right from the beginning, with Directive 2001/83/EC.

Definition of wholesale distribution of medicinal products:

All activities consisting of procuring, holding, supply or exporting medicinal products, apart from supply medicinal products to the public. Such activities are carried out with manufacturers or their depositories, importers, other wholesale distributors or with pharmacists and persons authorised or entitled to supply medicinal products to the public in the Member State concerned.

From this definition, we see that Manufacturers also can undertake wholesale distribution of medicinal products covered by their manufacturing authorisation.

Dir 2001/83/EC article 77(3):

Possession of a manufacturing authorisation shall include authorisation to distribute by wholesale the medicinal products covered by that authorisation.

Now what do the GDP guidelines 2013/C 343/01 say?

2013/C 343/01, Introduction paragraph 9:

Possession of a manufacturing authorisation includes authorisation to distribute the medicinal products covered by the authorisation. Manufacturers performing any distribution activities with their own products must therefore comply with GDP.

What does this mean to the QP?

If the QP is named on the manufacturing authorisation of a manufacturer that also undertakes wholesale distribution of medicinal products covered by that manufacturing authorisation, the QP must ensure that the distribution activities comply with GDP.

For the wholesale distribution activities performed under the manufacturing authorisation, the QP fulfills the role of the "Responsible Person" as described in chapter 2.2. of the GDP guidelines.

Why does Annex 16 only talk about QP oversight of the supply chain up to finished product certification?

Well, that's simple - Annex 16 is entitled "Certification by a Qualified Person and Batch Release". Therefore, the scope of Annex 16 ends with batch certification and release to saleable stock.

The next stage after release to saleable stock would be distribution of the finished medicinal product, which is covered in detail in the GDP guidelines 2013/C 343/01.

Summing up:

When considering the extent of the responsibilities of the QP, we should not only look at Annex 16, but go back to the ground rules, which are laid out in Dir 2001/83/EC, then work back up, lining up the pieces of the different directives and guidelines. The responsibilities detailed in Annex 16 are only with respect to QP certification and batch release, while the full extent of QP responsibilities goes further than that.

QA and Supply Chain

Sun, 21 Nov 2021 19:15:54 GMT

Why is it important for QA to know the supply chain of materials and products?

In my early days learning about risk management and quality oversight, I was advised to develop a "helicopter view" of the "landscape", before zooming in on the details. To develop the "helicopter view", I found it very useful to literally build overviews of whatever subject was forming my "landscape". This was applicable to practically everything I wanted to learn - systems, processes, organisations. It enabled me to identify connections between systems, processes and organisations, as well as potential risk areas.

When I became a QP and RP, the first thing I wanted to understand was the supply chain of the products I was responsible for. Convincing the Supply Chain Department that they could safely provide me with all the information without me poking my critical QP nose into their business proved a little challenging, but slowly I got the bits of information I wanted, to improve my understanding of what I was actually responsible for - what I was signing for when I released each product batch, and how the Supply Chain Department was supporting me in fulfilling my QP and RP responsibility of ensuring continuity of medicines to patients who need them.

Some product supply chains were relatively straightforward - one raw material supplier, in-house active ingredient / drug substance manufacture, progressing to in-house bulk drug product manufacture and then to final packaging. Some were fascinatingly complicated - multiple raw material suppliers, different manufacturing sites involved in drug substance and drug product manufacture, multiple testing sites for different stages of production, multiple final packaging sites and multiple storage locations before distribution to customers.

The more I learned, the more intrigued I became. Happily, I had the opportunity to transition from QA to Supply Chain, to be part of the business discussions and understand the complexities that result in supply chains that might not seem logical from QA perspective, but are necessary from business considerations. My QA background gave me more depth to my role in ensuring successful launch of new products to the market, while my experience in supply chain added more breadth to my QA work in later projects.

My practice of piecing together supply chain overviews to develop this "helicopter view" has served me very well the last couple of decades, allowing me to quickly grasp the complexities of bringing a new product to the market, or gain a good estimate of the risk areas of a company that I'm working for.

I've managed to highlight business and quality risks with this "supply chain overview" approach and proposed actions to the managers involved, to reduce or mitigate the risks as well as put some QA support mechanisms in place.

My advice to all QA teams is to first get a high-level understanding of what the supply chain of the company is. Knowing how materials flow into and through the company to result in finished drug product in the hands of patients who need them is the first step in managing the quality risks associated with maintaining continuity of supply of the finished drug product, which is ultimately the responsibility of QPs and RPs, with the support of their QA teams.