We’re only just smoothing the surface of consumer skincare product personalisation. The current trend for products to be curated, customised, or even bespoke to some degree, simply the start. In the future, the industry will be driven inexorably in this direction by the development and marketing of next-generation products personalised to your specific skin microbiome.

Catch up with out last webinar on personalisation

I don’t detect much in the way of strong clinical evidence to back their claims, but some companies insist they are already doing this. You can read about a couple, Bebe & Bella’s Probiotic Line and Gallinee’s Happy Bacteria, in this article on microbiome cosmetics.

The personalisation trend has some thought-provoking consequences for supply chains and delivering products to market. I can foresee a two-stage journey taking us forward from today, where large batches of product are made at a defined manufacturing facility, typically at tonne scales. Stage one moves to small-batch manufacturing (kilogram scale) but still at defined facilities. Stage two then transitions to localised manufacture (gram scale) at the point of sale – an uncontrolled environment. Here’s what I mean:

Overall, we would expect the total quantities to increase, or at least stay the same. Thus, we have extreme fragmentation of manufacture (across several orders of magnitude!) along with the elimination of traditional methods to manage quality. Assuming the industry will head in this direction, let’s look at some practicalities. What consequences will this have in terms of manufacture?

Challenge 1: microbiology

In the EU, Regulation 1223/2009 requires testing to prove firstly no microbiological contamination in a given batch of product – the microbiology specification – and secondly, the formulation cannot support microbiological growth – the preservative efficiency test. Testing is done against recognised standards such as ISO 21149:2017 or ISO 11930:2019. The situation is similar in the US where the Federal Food Drug and Cosmetic Act prohibits marketing of adulterated product, which includes microbiological contamination.

Current solutions are based on batch testing. You make a big batch of product and test it to prove that it is both uncontaminated and unable to support growth. The tests are time-consuming (weeks) and expensive (hundreds of dollars / euros per batch). This approach is commercially viable when applied to large quantities, but it is not scalable. It does not work as batch sizes reduce because the fixed cost of testing is amortised across a decreasingly small amount of product. In our conversations with companies working on next-generation personalised skincare products, this lack of cost scalability in demonstrating microbiological safety is already identified as a key roadblock to commercialisation. We believe two new approaches are needed to get past this problem:

1. True rapid microbial testing for contamination. The last decade has seen the development of novel molecular biology methods for identifying microorganisms from their DNA. Of particular interest are enzymatic amplification techniques. Tiny amounts of DNA can be detected in a few minutes in a simple assay without needing complex instrumentation. These approaches could provide a realistic route to low-cost rapid testing on small batches without needing dedicated labs.

2. Process validation to demonstrate lack of growth. Unlike contamination, testing preservation efficiency cannot be conducted with a rapid test. Preservation efficiency depends on the formulation and how well it is controlled during manufacture. Rather than testing the outcome, a process validation approach is needed where testing is performed on a range of formulations during development and strict limits defined where preservation efficiency is acceptable. During manufacture, you then prove the formulation was made within these defined limits and is therefore equivalent to the material you tested during development.

Challenge 2: distributed cGMP

Skincare products are made in current Good Manufacturing Practice (cGMP) compliant facilities. cGMP provides a long-established, well-proven set of rules and principles to ensure the manufacture of safe, high-quality product. A key part of cGMP is the management of facilities and staff: ensuring equipment is well-maintained and operating correctly, ensuring staff are trained and executing processes correctly.

Stage 1 transition to small-batch manufacture at a facility still allows this type of cGMP control, though maintaining quality with much more frequent changes of formulation is a challenge in its own right. But what happens at Stage 2 when you move away from a facility with trained staff, well-maintained equipment, quality supervisors and so on?

The need for quality does not go away. The only practical route forward is to move to much more automated equipment that delivers quality without human intervention. The kind of issues that need consideration are minimising user interactions, simplifying user interactions, robustly defining critical quality parameters, and integrating measurements that monitor the key parameters and ensure long-term performance. And, of course, the cost challenges. These sophisticated technologies must be delivered at a viable cost for the business.

Learning from healthcare and pharma

These challenges have exact parallels in healthcare and pharma. First, let’s look at point of care (POC) in-vitro diagnostics (IVDs). These are low-cost consumer-style devices designed to perform accurate microbiological measurements right by the patient, wherever she or he happens to be – at home, in an ambulance, at a clinic.

This move to POC from traditional lab-based testing – which brings great benefit in timeliness of results to guide patient care – has driven innovation in sensing, integration, automation, cost reduction and ease of use. All could be applied to the microbiology issues in skincare product manufacture. There is a guidance document, issued by the Federal Drugs Administration (FDA) in the United States defining something called ‘CLIA Waiver’. Basically, this is what you need to do to make an IVD so simple and reliable an untrained user can get an accurate result.

The second area to learn from is Advanced Therapy Medicinal Products (ATMPs). These are the next generation of therapeutics where you engineer a patient’s own cells to become the therapy. The best-known example presently is Chimeric Antigen T-Cell therapy (CAR-T). In 2017 two drugs of this type, Kymriah® and Yescarta®, achieved first market approval for Acute Lymphoblastic Leukaemia based on outstanding clinical results.

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A big challenge today for these therapies is scale-up and manufacture. There is huge interest in this industry to develop distributed manufacture processes to increase availability globally and reduce cost. There is a lot of work going on today looking at ways to ensure quality and deliver cGMP compliant processes in a distributed context through methods such as Quality by Design and integrated Process Analytical Technologies. The consumer skincare industry is not alone!

To conclude, I think there is good reason to believe the manufacture challenges arising from increased personalisation can be addressed. But achieving this requires rethinking from the ground up on how safety is demonstrated, and processes controlled. Here, the industry will gain much from learning from the healthcare sector to piggy-back on new ideas and approaches. However, the more challenging cost base in consumer products compared to healthcare demands further radical innovation in equipment and measurement methods.

執筆者
Richard Hammond
Technology Director and Head of Bioinnovation