Personalized drugs transform the way authorities handle GMP

Managing Consultant, Compliance Consulting, NNE

Monica Hueg

Managing Consultant, Compliance Consulting, NNE

Monica Hueg has more than 15 years of experience with biotech, pharmaceuticals and the construction and production of medical device facilities. Monica’s focus is on facilitating strategic business decisions with special attention to quality and compliance. She consults on strategic planning for future production and quality improvements, often in connection with compliance gap analysis/assessments.

Monica has extensive theoretical insight and practical experience within GMP and compliance. She is involved in the analysis, planning, implementation and completion of a wide range of projects within the pharma industry globally. Monica regularly teaches courses within GMP and compliance and she has developed a number of courses within the topic.

"One-size fits all" no longer applies to the world of pharmaceuticals. With the increase of personalized medicine, manufacturers are pressuring regulatory authorities for faster product approval. But what else have personalized medicines changed in the GMP world?

Today, a better understanding of genetics as well as faster DNA sequencing allows doctors and scientists to provide better diagnoses, safer drug prescribing and more effective treatments. This is done by tailoring medicine to a single patient with personalized medicine [1] , also known as "targeted medicine". These developments give individuals increased control over their health. But the road to effective and safe personalized medicine is filled with challenges related to good manufacturing practice (GMP).

GMP compliance is essential to ensure the quality of medicinal products. The intrinsic characteristics of personalized medicine, such as Advanced Therapy Medical Products (ATMP)[2] include variability of the starting materials, small batch sizes, short shelf life, and so on. These qualities pose specific challenges for the manufacturing process.

Additionally, early phases of research may take place in a hospital setting operating under a different quality system than those typical of the pharmaceutical sector (as given in the ICH Q10). This creates a gap of adequate systems in which to evaluate the quality of starting and raw materials. This is when personalized medicine changes the healthcare industry game – not only in the way many severe diseases are treated, but also in the way medicine is developed, approved, produced and marketed.

Focus shift in personalized medicine

A keen focus – and a challenge – for advanced therapy medical products is GMP compliance within research, development and manufacturing. However, recently, this focus has shifted. In 2015, GMP regulatory and compliance was all the industry could talk about. Later, in 2016, the main focus was on primary manufacturing of ATMP and secondly on GMP regulatory topics and challenges. Today, the trend leans towards manufacturing, new concepts and technologies rather than solely GMP.

The evolution of new concepts for future ATMP facilities and processes centres on the same trends we see in the large-scale pharma industry: closed systems and processes that move operators away from direct product contact and minimize product quality risk, and automation that enables the downgrade of GMP levels.

Personalized medicine changes the healthcare industry game – not only in the way many severe diseases are treated, but also in the way medicine is developed, approved, produced and marketed.

Monica Hueg, Managing Consultant

Towards the batch of one

When using the patient’s own cells to create a treatment for that specific patient, only one batch is used. This is due to both the use of the patient's unique cells and the patient’s illness, which strictly limits the opportunities to re-do the procedure. This paradigm creates challenges on how to make these therapies commercially viable and GMP compliant, such as:

  • Manufacturing capacity
  • Manufacturing reliability
  • Manufacturing cost
  • Manufacturing flexibility/scalability
  • Comparison of test results
  • Classification of rooms
  • Patient related logistics
  • Regulatory approval of processes and product
  • Cleaning
  • Cross contamination / mix-ups
  • Quality control
  • Safety for the operators
  • Safety for the patient
  • From lab to the market
  • Batch release
  • Traceability

Full cGMP compliance is a requirement throughout every process step for manufacturing facilities for personalized medicine. However, it is important to note that today’s GMP regulation was born out of pharma blockbuster manufacturing scale and does not conform to personalized medicine production. For example, personalized medicine requires much faster approval. Authorities are working with a set of regulations that are more flexible and can embed the production of personalized medicine.

The European Medicines Agency (EMA) drafted a stand-alone guideline with special focus on ATMP in 2015 Consultation Document – Good Manufacturing Practice for Advanced Therapy Medicinal Products. The revised framework aims at introducing flexibility for ATMPs.[3]

In 2013, the US Food and Drug Administration (FDA) published a report Paving the way for Personalized Medicine: FDA’s Role in a New Area of Medical Product Development, reaffirming the agency’s ongoing commitment to this emerging area of medicine by addressing personalized medicine from regulatory perspectives. There is still much to be done, but the agency strives to evolve its regulatory processes in response to and in anticipation of scientific developments that are critical for the development of personalized medicine.

Progress has not been swift, but the authorities are giving significantly more attention to personalized medicine and how to overcome inherited GMP obstacles in the current regulation. There will be many more regulatory changes in the near future to keep up with the expanding market, and the way GMP challenges are tackled globally will be a key influence over the future of personalized medicine.

[1] A broad term covering many different areas, no commonly agreed definition of the term yet but widely understood personalized medicine refers to three main categories; biomarker-based drug with co-diagnosis, gene therapy and cell-based therapy

[2] Advanced Therapy Medical Products include, among others, cell and gene therapies

[3] Per EU regulation 2007 (EC 1394/2007) all ATMPs are regarded as medicinal products and must therefore comply with current EU drug legislation including GMP requirements. The last contribution had the deadline of September 2016. The final version is in progress, but no deadline is published.