PCMO Initiative Gathers Strength

In June 2008, the Parenteral Drug Association (PDA) Board of Directors approved the development of a new initiative called the Paradigm Change in Manufacturing Operations, or PCMO^SM for short. The goal of the PCMO program of activities is to provide an overarching framework for topics which will become the subject matter of future PDA technical reports and other documents and training events.

Richard Levy

Background

By virtue of the PCMO governance, there is a steering committee made up of PDA Advisory Board members and as well as a number of task forces. As part of the PCMO governance process, each topic is prioritized to maximize the value of the expected deliverables to pharmaceutical manufacturers of investigational medicinal products (IMPs) and commercial products.

The steering committee has developed a portfolio of current deliverables (see Table I) to facilitate the implementation of the guidelines from the International Conference on Harmonization (ICH) guidelines Q8 Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.

Table I: PCMO project portfolio.

Generally on PCMO project teams, an effort is made to incorporate membership from small, local to large, global pharmaceutical and biotechnology companies, technology enablers, and, in some cases, regulators from the US and Europe. There is an understanding among participants that PDA is working toward the common objective of delivering output that embodies the best experiences of our members and, in so doing, creating consensus-based approaches that are not only grounded on ICH principles, but also are pragmatic and scalable such that they can be implemented by any size of company.

PCMO projects

The PCMO portfolio of projects follows the product life-cycle concept and has the following broad strategic intent:

• Enable an innovative environment for continual improvement of products and systems

• Integrate science and technology into manufacturing practice

• Enhance manufacturing process robustness, risk-based decision-making and knowledge management

• Foster communication among industry and regulatory authorities.

Accordingly, PCMO projects have been grouped into four broad categories: life-cycle approach, quality systems, process management, and quality risk management. These categories are also consistent with ICH guidelines and with the focus of the majority of PDA technical reports and ongoing projects. There are currently 19 PCMO projects in progress (see Table I). Additional projects will be added as necessary to satisfy the needs of the industry as recognized by PDA membership and approved by its Advisory Boards.

Progress has been made on several projects already, and many will be completed this year. The following section highlights some of this work.

Q01–Knowledge Capture. According to ICH Q10, knowledge management is defined as a systematic approach to acquiring, analyzing, storing, and disseminating information related to products, manufacturing processes and components. It is expected that complex information is captured, managed, and shared during the product life cycle. The Q01 PCMO technical report focuses on the continuum of data collection through to understanding of both the process and product and will consider the feedback loop of decision-making. Aspects included in the draft report include explicit knowledge, converting tacit knowledge (nonwritten personal knowledge of employees), and the means of capturing knowledge from data interpreted as information. The draft will focus attention on collecting prior knowledge from experience, which can include experience obtained from similar processes (e.g., internal knowledge, industry scientific and technical publications), published information (e.g., external knowledge: literature and peer-reviewed publications), pharmaceutical-development studies (e.g., mechanism of action, structure/function relationships), technology-transfer activities, and process-validation studies as well as other downstream life-cycle sources. There is much to learn and the technical report will provide guidance in this regard.

P01–Process Validation and Verification: A Life-cycle Approach. Great progress has been made by the PCMO Process Validation and Verification task force. As with other PCMO deliverables, this report focuses on process validation and continued verification, and is being optimized for global use as recommended in ICH Q8, Q9, and Q10 (the product life cycle). A key task-force goal is to promote the implementation of process-validation concepts from a practical perspective.

The scope of the PCMO validation technical report includes all drug products included in the FDA January 2011 guidance on process validation (e.g., pharmaceuticals, both sterile and nonsterile; biologicals, active pharmaceutical ingredients [APIs]; radiopharmaceuticals; and veterinary drugs). It also includes the drug-product component of combinations of drug and medical device. Consistent with FDA guidance, this technical report will exclude medical devices, dietary supplements, medicated feed and human tissues, as well as cleaning validation because cleaning is covered in other PDA technical reports (TR-29 and TR-49).

The bottom line is that this technical report is intended to assist in the design and execution of process-validation studies to ensure the reproducibility and robustness of the processes. The report is not intended to be all encompassing. Other means of approaches or even traditional process validation may still be applicable in some regions of the world. PDA anticipates publishing this document at the end of 2011.

P04–Utilization of Statistical Methods for Production and Business Processes. As manufacturers seek to improve quality, statistical methods have been rediscovered as crucial tools for the successful development and manufacture of pharmaceutical products. Manufacturers seek to consistently produce products that conform to predetermined quality characteristics, and statistical methods have shown value in providing objective evidence toward meeting this goal. ICH, the International Standards Organization (ISO), and the European Union have provided guidance on the use of statistical methods.

The primary objective of the PO4 task force is to convey the appropriate use (for each application) of statistical methods at a level that most industry users can understand. The purpose of the technical report is to present relevant and easy to use statistical process control methods that are applicable to our industry. Advanced statistical methods, such as multivariate models and design of experiments (DoE), will not be considered. The team has completed its first draft of the technical report and will begin the final review process in the second quarter of 2011.

R01–Risk-Based Manufacturing. PDA's 2008 Technical Report No. 44 Quality Risk Management for Aseptic Processes provides an excellent case study for aseptic processes. The PCMO task force on risk-based manufacturing is expanding the concepts presented in TR-44. Specifically the task force is charged with defining an approach for implementing quality risk-management (QRM) practices that are grounded in ICH Q9 principles. The task force is divided into four teams that are working on multiple deliverables, including implementation details for a QRM program for manufacturing operations and specific case studies. This new content will provide "how-to" details for implementing an integrated QRM program for manufacturing operations.

Additionally, there are three supporting teams developing specific risk-assessment case studies for biotech manufactured APIs, drug product (liquids and solids), and packaging & labeling. The case studies will use the concepts discussed in the QRM implementation document and have been selected to illustrate the use of various risk-assessment tools for different types of manufacturing operations.

To close, the projects highlighted above are expected to conclude this year. As we move into 2012, PDA will have a plan for bringing to completion additional PCMO projects. We expect to report in more detail on these and other projects in Pharmaceutical Technology in Fall 2011.

Richard Levy, PHD, is senior vice-president of the Parenteral Drug Association (PDA), levy@pda.org.