March / April 2018

ISPE Regulatory Volunteer Operations Part 2

Carol Winfield

In my last column,1 I introduced the Regulatory Steering Committee, which was convened to provide guidance and oversight for ISPE’s regulatory committees and initiatives. This column focuses on the committees and groups that carry out this important work in accordance with the ISPE Strategic Plan.


Formerly the Regulatory and Compliance Committee, the Regulatory Quality Harmonization Committee is comprised of a management team called “RQHC Global” and regional focus groups (RFGs).

RQHC Global supports the RFGs by coordinating regional initiatives and ensuring a global approach is taken where needed. It also coordinates ISPE responses to new and draft regulatory documents by selecting documents for comment, identifying subject matter experts within the Society to develop ISPE’s response, and overseeing the comment process to ensure it remains transparent and aligned with members’ interests. In addition, RQHC Global supports ISPE education by developing regulatory/quality tracks and panels at ISPE’s international conferences and Annual Meeting.

RQHC’s current RFGs are Asia-Pacific, Europe/ Middle East/Africa, and North America, with plans to reestablish a group in Latin America. The RFGs are tasked with maintaining ISPE’s currency in global regulatory environments, establishing and growing regulatory relationships in their regions, and advancing ISPE’s visibility with key regulators. RFGs assemble task teams as needed to explore potential regulatory, quality, and compliance opportunities, and recommend approaches for ISPE’s involvement or response. RFGs also arrange informal meetings with regulators to identify areas of concern in which ISPE may be able to provide expertise.


Facilitate industry-wide clarity of new applicable regulations on regulatory matters relevant to ISPE’s attention and expertise, advising on impacts and resolving towards solutions, seeking harmonization of regulatory expectations where desired and possible.


ISPE’s PQLI® initiative was established to provide guidance on the implementation concepts described in ICH guidelines Q8, Q9, Q10, and Q11. To this end, the committee has published four Good Practice Guides to provide global solutions for these challenges. It helps ensure product quality throughout the product life cycle, with a view to continuous product improvement. The committee also addresses significant new regulatory-focused topics and issues that affect both small and large molecules, across dosage forms.

PQLI technical subteams are working on the following topics:

Expedited Programs for Patients

Expedited therapy designation has resulted in numerous approvals contingent upon post-approval commitments, including clinical studies, stability, and managing global supply chain to assure medicinal product availability. Uncertainty around implementation of elements of product-control strategies has created perceived risk to firms pursuing accelerated development submissions as well as life cycle management post approval, with the potential of impeding timely access to novel medicinal products. This team is engaging industry and regulators for open discussion of the challenges of entering accelerated development programs, developing best practices to enable improvements in future submissions to benefit both industry and regulators.

Clinically Relevant Specification (Patient-Focused Quality Standards)

This sub-team is developing strategies and practical solutions for establishing appropriate product- quality standards focused on patient safety and efficacy. Its scope includes understanding patient needs, appropriately designing product quality profiles, deep understanding of the formulation and manufacturing process, and establishing appropriate specification, which links to patient safety and efficacy. Focusing on drug substance and drug product impurity specification as a first step, the group will gradually expand to other critical quality attributes and more advanced therapeutics, including biotech products.

Continuous Manufacturing

Created to coordinate regulatory and scientific efforts, the Continuous Manufacturing team provided comments for the US Food and Drug Administration(FDA) docket “Submission of Proposed Recommendations for Industry on Developing Continuous Manufacturing of Solid Dosage Drug Products in Pharmaceutical Manufacturing.” The comments offered ISPE’s view of desired content in future FDA or international guidance on continuous manufacturing for solid oral dosage forms. The team also plans to produce implementation papers.

Knowledge Management

This team is researching how the pharmaceutical industry is leveraging knowledge management, an ICH Q10 enabler. It intends to share case studies and develop industry best-practice guidance.

Process Capability

Both FDA and the pharmaceutical industry have advocated recently that process capability become more mainstream. Formed in 2015, this team is dedicated to advancing the use of process capabilities in the pharmaceutical and biotech industries. Members have written two articles. “Role of Process Capability in Monitoring Product Quality,” a concept paper, is available on the ISPE website.3 More recently, team members developed a process capability maturity model tailored to our industry that was published in the January-February 2018 issue of Pharmaceutical Engineering.4 This model should help life sciences executives set up process capabilities programs within their own organizations and compare them to those of peer companies.

Process Validation

The Process validation (PV) team has spent the last seven years working to advance implementation of the life cycle approach to process validation by addressing its most difficult aspects. The team has issued eight discussion papers, with topics that include determining and justifying the number of PV batches, developing CPV monitoring plans, implementing the life cycle approach at contract manufacturing sites, and applying the life cycle approach to both biotech manufacturing and packaging validation. These are available on the ISPE website at:

The team has held nine conferences, including the recent Process Validation Conference, which focused on continued and ongoing PV plan development, and the Statistics in Process Validation Conference, which focused on statistics in support of all stages of the PV life cycle. Team members have also contributed to a three-day training course on implementation of the life cycle approach to PV which covers PV-related aspects of product development, the validation exercise, and ongoing process verification following PV. Over the past year, they have compiled a comprehensive PV Good Practice Guide, which is slated for publication in 2018.


Initiative teams are convened to address broad topics that are regulator driven or regulatory focused.

Quality Metrics

The Quality Metrics/Advancing Pharmaceutical Quality team was created in 2013 following an FDA request for ISPE’s views on measures of product quality, site quality operations, and systems performance. The team’s resulting activities have enabled ISPE to provide objective, data-driven input to the FDA, European Medicines Agency, and other regulators on standardized metrics reporting. The team partnered with McKinsey and Co. from 2014–2015 to conduct the industry’s first quality metrics pilot program. The results, along with industry input obtained at ISPE summits and conference sessions lead by the team, informed ISPE’s comments on FDA draft guidances “Request for Quality Metrics”5 and “Submission of Quality Metrics Data,”6 as well as the “Quality Metrics Technical Conformance Guide—Technical Specifications Document; Availability.”7 The pilot data continue to provide a valuable source for additional analysis in response to FDA requests.

Building on pilot data that identified relationships between organizational culture and quality outcomes, the Cultural Excellence subteam examined the influence of an organization’s culture as an enabler of quality outcomes. In 2016 the subteam published the “Cultural Excellence Report,” which was presented in conjunction with a two-day conference on the topic. The conference and report offered original approaches, practices, and practical tools to promote behavioral change that will ultimately benefit patients and businesses.

In 2017, the team held two industry workshops for knowledge exchange on quality metrics that were designed to advance industry/regulator dialogue beyond written feedback to face-to-face conversations on achieving the FDA’s vision of a “maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drugs without extensive regulatory oversight.”2 The team is now expanding its focus from the agency’s proposed reportable metrics program to the integration of culture, operations, and operational excellence for a complementary approach to advancing the state of pharmaceutical quality to benefit industry, regulators, and patients alike. This innovative work will be highlighted in a Pharmaceutical Engineering Special Report on Quality Metrics in the September-October 2018 issue.

Drug Shortages Initiative

For nearly a decade ISPE has facilitated communication between the industry and health authorities on the subject of drug shortages. The Drug Shortages Initiative team is committed to promoting programs and tools to assure the continuous availability of quality pharmaceuticals to patients. The team also promotes drug shortages prevention through ISPE’s Facility of the Year Awards program by recognizing companies that have strengthened their ability to prevent drug shortages or minimize their effects on patients.

In 2013 the team launched a comprehensive survey to gather data on the technical, scientific, manufacturing, quality, and compliance issues that have resulted in drug shortages. Results were published in the “Report on ISPE Drug Shortages Survey.” Follow-up publications included the “Drug Shortages Prevention Plan,” which detailed recommendations for avoiding or mitigating drug shortages, and the “Drug Shortage Assessment and Prevention Tool,” a system for actioning the prevention plan.

In 2017 the team collaborated with the Pew Charitable Trusts to publish “Drug Shortages: An Exploration of the Relationship between US Market Forces and Sterile Injectable Pharmaceutical Products.”

For more information on any of the groups, contact Carol Winfield, ISPE Director of Regulatory Operations, at cwinfi