Looking at Trends in Parenteral Manufacturing

As part of Pharmaceutical Technology’s 40^th Anniversary issue, which will be published in July, the editors interviewed industry experts about the biggest changes the industry has seen in the past 40 years and what they foresee for the future. The trend toward specialized medicines focused on smaller patient populations is leading to smaller production batches and a greater need for flexibility in manufacturing equipment and systems, says Bernd Stauss, senior vice-president of Pharmaceutical Production/Engineering at Vetter Pharma-Fertigung. The increase in highly potent drugs is another driver for equipment advances, notes Christian Treitel, director, Business Development Pharma, Bosch Packaging Technology. Pharmaceutical Technology spoke with Stauss and Treitel about developments in parenteral manufacturing and fill/finish.

PharmTech: What have been the most significant changes in parenteral pharmaceutical manufacturing and fill/finish in the past 40 years?

Treitel (Bosch): In the past 40 years, we have seen significant increases in automation and the use of barrier systems like restricted access barrier systems (RABS), closed RABS, and isolators. More complex processes can be managed, product quality has improved, and operating costs have been reduced. A wider variety of packaging styles-ready-to-fill syringes and, recently, vials and cartridges-and flexible machine platforms offer pharmaceutical manufacturers the flexibility for different products and requirements. Pharmaceutical manufacturers also more often require 100% in-process checkweighing to prevent product loss of expensive drugs.

Stauss (Vetter): The primary development in parenteral pharmaceutical manufacturing we have experienced over the past 40 years has been the continuous improvement in the quality of the drug manufacturing process. This has had an impact on the entire bio/pharmaceutical industry supply chain. Over this time period, automation grew rapidly and continues to do so today. At Vetter, for example, the use of robots in the production process had already begun by the 1990s.

From a technological aspect, single-use technology is an emerging trend in the fill-and-finish segment, primarily in the early phases of a drug-development project. A large part of the industry, however, does not believe that single-use equipment will replace stainless-steel technology as a whole. Nevertheless, single-use technology offers a valuable option within special fields of the production process. In our experience, both technologies have their individual pros and cons.

Today, we see two specific leading cleanroom technologies on the market: RABS technology and isolators. RABS achieves the sterility assurance level (SAL) required by regulatory authorities and allows for rapid product changeover along with high safety. To better meet future industry trends in quality, safety, and flexibility, combining the advantages of both isolator and RABS technology appears to have promising potential for a contract development and manufacturing organization like Vetter. An improved RABS concept, called Vetter CleanRoom Technology (V-CRT), achieves fast and fully-automated decontamination of the cleanroom using hydrogen peroxide.

PharmTech: What trends or new developments do you foresee for the near future?

Stauss (Vetter): One of the primary developments we see is the increase in the overall complexity of individual drug substances which, in turn, affects all parties along the supply chain that are involved in the handling and processing of these substances. Expectations for quality are high, with customers demanding a significant level of oversight.

Patients are asking for innovative drug-delivery systems that fit better with the ‘mobile lifestyle’ of today. Having access to those systems supports their individual acceptance and compliance. Large areas of the developed world are experiencing growth in aged populations, which has resulted in an increase of associated diseases. As they can often be treated in private settings, there has been an impact on the homecare sector, thus creating a need for appropriate devices, such as pens and autoinjectors. Finally, we have experienced an increase in topics such as digitalization.

Treitel (Bosch): In order to further reduce or avoid human interventions, there will be fully automated production lines with the use of robotics. Connected industry solutions will bring more intelligence into production. These technologies will help achieve higher productivity, safety, and efficiency.