Engineering, Validation, Automation and Service Companies in the Pharmaceutical Manufacturing Ecosystem

Introduction

The COVID-19 crisis has emphasized the need for a pharmaceutical industry capable of developing new products to respond to public health emergencies, as well as increasing the production of essential medicines. The pharmaceutical industry is now seen as an important element in national security.¹ Advanced pharmaceutical manufacturing could provide manufacturing flexibility and agility to respond to sudden increases in product demand.² Advanced pharmaceutical manufacturing, including continuous manufacturing, is also recognized as a means to improve product quality and reliability, and eventually mitigate or reduce drug shortages.^2-4

Continuous direct compression is now considered a technology that has graduated from the FDA’s Emerging Technologies program. The term “graduation” has been used to describe the process through which the Emerging Technology Program (ETP) “transfers review responsibility of future application submissions from ETP to the standard quality assessment process".⁵ This “graduation” is possible because additional reviewers of the technology have been trained within FDA. In the same manner, additional training efforts are needed for pharmaceutical manufacturing sites to adopt continuous manufacturing.^6,7

A recent grant from the Economic Development Administration made it possible to provide training through a Mobile Training Unit for Process Analytical Technology and Continuous Manufacturing to over 100 pharmaceutical personnel in Puerto Rico.⁸ The project took into consideration that the pharmaceutical workforce includes the small companies that provide engineering and validation services to large pharmaceutical manufacturing sites. In this project, the companies were initially called engineering and validation service companies. However, several companies emphasized that they also perform automation projects and provide an array of services such as consulting and subcontracting. The term Engineering, Validation, Automation, and Service companies (EVAS) was then developed to encompass their efforts. The trainings were offered to personnel from 13 pharmaceutical companies and eight EVAS.

The personnel at a pharmaceutical manufacturing site will include the companies’ employees and contract personnel from EVAS. The contract personnel may be on site for just a few hours, to perform maintenance on a liquid chromatograph, calibrate analytical balances in the Quality Control laboratory, provide emergency troubleshooting support to a PLC Automation control system, or provide custom Automation systems training. However, they may also spend several months installing new manufacturing equipment. These installations require operational qualifications and the development of procedures for the use and maintenance of the equipment. Additionally, they may contribute to the validation of the manufacturing process that uses the new equipment. Also, EVAS contract personnel may support the justification, definition, planning, and implementation of site capital projects, including budgetary estimates generation, system lifecycle documentation generation, automation hardware design, assembly and installation, automation software code development and integration, and Manufacturing Execution Systems (MES) recipe authoring. Moreover, EVAS resources may supplement pharmaceutical site personnel in providing 24/7 day-to-day Automation, IT, and MES support either on-site or on-call (remote). Also, industry-experienced EVAS personnel may serve as Project Managers leading complex process improvement, capacity increase, or regulatory compliance projects. These contract personnel may belong to a small to medium EVAS or be individuals who offer these services.

This article provides a summary of twenty-two interviews conducted with leaders (including CEOs and managers) and personnel of EVAS that have been developed in Puerto Rico, but which also provide services beyond the island’s beautiful coastline. This article provides a snapshot of an important sector in Puerto Rico’s pharmaceutical industry, in constant development for over 60 years and the largest provider of biopharmaceuticals to the US.⁹ The island has pharmaceutical exports of over $93 B, and has over 50 manufacturing sites, which provide close to 20,000 direct jobs with 12 of the world's top 20 pharmaceutical companies.¹⁰ The pharmaceutical products made in Puerto Rico are exported to over 130 countries.¹¹

Methodology

The study identified 67 EVAS located in different parts of the island. Representatives from sixteen of these companies were interviewed through a one-hour videoconference. Three interviews were conducted with employees from one of the companies. About half of the companies were already known to the researchers before the study started, and the others were identified during the study. Several companies were identified through Puerto Rico’s Registry of Corporations and Entities, and through sources using keywords such as engineering, validation, automation, automatization, service companies, and pharmaceutical service companies. The interviews also included two employees of non-profit institutions and a University professor with significant expertise in workforce development.¹²

All interviews were conducted following the procedures established by the Internal Review Board and the Human Research Subjects Protection Office of the University of Puerto Rico. This process was followed by a proposal written for this project, along with the certificate for Social and Behavioral Responsible Conduct of Research from the Collaborative Institutional Training Initiative (CITI) course taken by each of the members. Interviewees either signed a consent form or expressed verbal consent prior to being recorded, and after starting the recordings.

A question guide was developed before the interview. However, as the interviews progressed new important subjects were identified by the participants. Therefore, the interview guide was modified throughout the process.¹²

Results

The interviews included ten company founders. All previously worked in the pharmaceutical industry where they obtained the expertise needed to develop their companies. The study also included six contractors, two entrepreneurs, and one startup.

The companies offer a wide range of services such as:

• computer validation
• automation and control systems
• manufacturing execution systems,
• search for qualified personnel and provide project staff
• consulting on regulatory issues and development of quality systems
• alternative sources of energy (solar energy, natural gas, etc.)

The number of employees in these companies varied from 7 to 650, with three of the companies having over one hundred employees. Each of these companies had full-time personnel, and also personnel that were hired on a temporary basis as needed for new projects.

One of the more interesting aspects was that the participants frequently mentioned collaborating with other EVAS. The companies realized that they did not have all the resources for a specific project, and found it best to join a competitor who had the complementary skills. Therefore, the interview guide was modified to incorporate questions that explored collaboration, cooperation, cooperative, service industry cooperative, service industry collaboration, competition, collaboration, and collaboration between rivals, which yielded the term "coopetition". Thirteen participants have collaborations with their competitors (coopetition).¹³ Out of the thirteen, three indicated that they had subcontracted with their competitors more than once.

The level of experience of the personnel in the EVAS varied from entry-level to professionals with more than 20 years of experience. The interviews revealed that EVAS is often the first job opportunity for recent graduates. The companies have developed their own internal training for recent graduates. However, they also include personnel with extensive experience. The EVAS could be supplying a project manager for a high-impact project responding to senior managers or directors at the pharmaceutical manufacturing plant. The project manager could supervise the work of several contract personnel at the manufacturing plant. The contract personnel could also be highly specialized at the M.S. or Ph.D. level. The EVAS are part of an ecosystem where information flows among different entities as shown in Figure 1.

The study found that only three of the companies had been involved in Process Analytical Technology or Continuous Manufacturing projects, even though the companies interviewed had significant expertise in Automation. One of the companies has extensive experience in Process Analytical Technology, in quality systems, and in working with the FDA to achieve real time release testing. A consultant on continuous manufacturing, PAT, and real-time-release testing was also identified. Two companies had experience in performing installation and operational qualifications of near-infrared spectrometers which are frequently used in PAT applications. In 2022 several companies joined to organize a meeting on the digital Transformation of the Life Sciences Industry.¹⁴ The companies interviewed are interested in advanced pharmaceutical manufacturing and could become major players in its implementation.

The Pharmaceutical Entrepreneurial Ecosystem

The base of an entrepreneurial ecosystem is usually a core of well-established businesses with ample research and development and production activities, which act as magnets for talented human capital such as recent graduates.¹⁵ The manufacturing sites on the island have served as the base of the pharmaceutical entrepreneurial system.

Human capital is recognized as a key factor in the entrepreneurial ecosystem. As knowledge is embodied in employees, human capital is required for technology transfer and the creation of new ventures.¹⁶ The importance of human capital is clearly evident in this study as the ten company founders gained the experience to start their companies in the pharmaceutical industry. The flow of personnel from established firms to new ones and vice-versa is considered an essential characteristic of a regional economic ecosystem.¹⁷ The entire ecosystem involves the significant flow of information as exemplified in Figure 1.

The EVAS provides many of the services needed to start a new manufacturing operation or validate a new manufacturing process. They could play a key role in pharmaceutical reshoring efforts.¹⁸

They also offer an option to the outsourcing of products to contract manufacturing organizations. A company could continue manufacturing products in their facilities but with significant involvement of contract personnel.

This article has been based on twenty-two interviews and the identification of 67 EVAS. However, the number of companies is greater. Some of these companies are now well known,¹⁹ while others are just starting. The study has provided a snapshot of the current pharmaceutical entrepreneurial ecosystem. However, additional research is needed to understand how it continues to adapt and grow.

Acknowledgement

This study was made possible through project #:01-70-14889 funded by the Economic Development Administration. We also acknowledge the support of all the companies that provided information for this study.

References

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Author Details

Nashaly Valentin Román,1 Barbara Alvarado Hernández,2 Moraima De Hoyos Ruperto,1 and Rodolfo J Romañach2* - University of Puerto Rico at Mayagüez, 1 School of Business Administration, 2 Department of Chemistry, *corresponding author: [email protected]

Publication Detail

This article appeared in Pharmaceutical Outsourcing:

Vol. 25, No. 1

Jan/Feb/Mar 2024

Pages: 12-15