More than ever the factory of the future must consider the requirements of a permanently changing product portfolio. Mergers and acquisitions lead more frequently to product transfers and closing down of older factories. Variations on market demands and shorter product life cycles can turn big production volumes to smaller ones and the other way around. The block buster model is decreasing and the diversity of the product portfolio will be increasing. The impact on manufacturing facilities will be a higher complexity on all levels of activities.

Flexibility and Agility

As a consequence, new factories must be able to be flexible and to react in time on changing demands, changes in product portfolio and new regulatory requirements. Product change-over-times on machines and equipment must be drastically reduced without negative impact for patient health and safety or on regulatory compliance. Single use technologies will be used as one lever. Investments need to be planned diligently and as late as possible in order to meet changing market demands in time. This requires excellence in project management. The factory of the future might be modular in order to be able to reconstruct one part while continuing the production in the other part.

Technology Platforms and Integration

Industry 4.0 will provide a lot of innovative impulses: End to end integration of computerized systems along the value chain, digitization and automation. As a premise data integrity must be ensured and respected in all functions of a pharmaceutical company, including finance/controlling and human resources. Integrated systems allow disclosing additional saving potentials not achievable so far in a world of „silos“.

Readiness for Innovation in Manufacturing

Some products of the legacy product portfolio will not be ready for a transfer to the new Industry 4.0 or Pharma 4.0 world as the product design and the related production processes are not suitable to be transferred into an automated process. They were developed in order to meet other target profiles and need to be re-developed or upgraded in a more or less time and cost consuming change management process.

How Authorities Evaluate Innovation

One of the most innovative approaches to regulators seems to be continuous manufacturing, in particular in biotechnological production and in the production of small molecules and active pharmaceutical ingredients. Processes can be shortened, the availability of drugs in the market can be increased, what is of essential interest for the health agencies.

Another sector is using new technologies for „personalized medicine“ which drives technologies suitable to make small and smallest batches. Early in the maturity process are trials with 3D printing of unit doses. „Galencial science“ is still to be developed, e.g. sustained release from such dosage forms.

More advanced are „single-use“ technologies which eliminate expensive cleaning validation, often reason for findings in GMP inspections when not performed correctly.

In principle, regulatory agencies welcome innovation when quality and safety is not compromised or even stabilized. Very often, new approaches lead to many questions from regulatory reviewers perceived by the applicant like „acts as a brake“. Therefore the innovator must spend energy in communication and explain also for technical non-experts the plausibility and the quality risk management concept of the innovation.

Continuous Manufacturing: A Future Common Practice?

Where continuous manufacturing will disclose advantages a trend has been established. Big volume and high value products can absorb the cost for investment in continuous manufacturing. For small products suitable processes via miniaturization of equipment must be developed.

The general advantages lies in avoidance of any problem linked with scale-up development, e.g. changed physical parameters in big reactors or high volume tablet machines compared with those from the equipment used in development.

Challenges of Implementing Mass Serialization Processes

The implementation of 2D matrix codes on packaging is not a new technology. The challenge for the pharmaceutical industry is more linked with the complete integration of all computerized systems along the value chain between starting materials and finished goods dispensing place (e.g. pharmacy), as this is the distance for verification of potentially falsified medicines. The integration of computerized systems is based on technical standards as defined in GAMP (Good Automation Practice) guidelines from ISPE, not only standardized product codes. Such technical communication standards must also consider the ownership of different parts of the product code, e.g. Global Trade Identification Numbers (GTIN) have other owners than national codes in the same product identification system. Some industry consortia work on these questions, e.g. OPEN SCS.

Advanced Aseptic Processing

The Pharmaceutical Industry is currently waiting for the first regulator’s draft on the complete revision of Annex 1 EC GMP Guide expected for late 2017. Therefore the discussions focused on progress on known areas of technology, e.g. when is the use of isolators indicated and where the use of RABS (Rapid Access Barrier Systems). How far can manual interventions be circumvented in aseptic filling processes? Which options for the use of robots do exist? Where is the advantage of single-use technologies? How can multi-purpose factories be safely run on the basis of RABS?

Data Integrity Is Key

New regulations from the Medicines and Healthcare products Regulatory Agency (MHRA), the World Health Organization (WHO) and the Food and Drug Administration (FDA) drive intensive discussions at industry. Companies have realized that data integrity is a hot issue for the entire value chain, as almost everywhere compliance-relevant data are handled. Correctness, completeness and distinctiveness of data are also parameter of GMP, therefore data integrity can be considered like „GMP for data“. Triggered by this, many companies have started standardization of data warehouses and also started frameworks for Master Data management as these are enablers for successful implementation of data integrity requirements.