The Power of a United Voice: How ISPE Members Can Help Shape Regulatory Guidance

When health authorities release drafts of new regulation and guidance for public comment, anyone is free to share their thoughts as an individual. But there is power in speaking with a united voice, especially when that voice belongs to ISPE.

“If my comments go in under the ISPE heading, they're carrying a lot more weight and gravitas,” said Charlie Wakeham, Director at WakeUp to Quality in Australia and Global Chair of ISPE GAMP®. “They go in with Mike Martin’s signature and the ISPE logo, the regulators take note.”

ISPE’s commenting process also gives members a chance to weigh in on documents that aren’t open for public comment, since health authorities sometimes solicit comments from only a select group of stakeholders including ISPE.

Regulatory commenting is important to ISPE and its members because it helps to prevent the adoption of unclear or ambiguous regulations. Regulators do their best to craft documents that will safeguard patient safety without stifling innovation or creating impossible conundrums for industry, but they can’t anticipate everything. They need help from experts with outside perspectives and on-the-ground experience.

“When a regulation is not effective enough, how much money do we all need to spend? How much extra effort and potential risk to the patient? If we have the right community commenting on a regulation before it is out, we have really a great benefit to the whole ecosystem,” said Teresa Minero, Founder of the consulting and digitalization firm LifeBee, now Strategic Advisor for ProductLifeGroup Company (PLG) and the ISPE Board of Directors.

THE COMMENTING PROCESS AT ISPE

ISPE provides comments to health authorities all over the world, including the US Food and Drug Administration (US FDA), the European Medicines Agency (EMA) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S). When members see a new document that ISPE may want to comment on, they can send it to RegulatoryComments@ISPE.org. Wendy McGhee, Health Authority Outreach Manager, Regulatory Affairs, for ISPE and ISPE’s project manager for regulatory commenting, shares the suggestions with the five-member Comment Coordination Team and two regulatory advisors, who decide whether the document is within the scope of ISPE and relevant to its members.

Once the Comment Coordination Team and regulatory advisors give the go-ahead, McGhee reaches out to the relevant ISPE regulatory committees and communities of practice, which in turn decide which subject matter experts to bring on board. Anywhere from 20 to 2,000 members may contribute suggestions on a given document. The individual comments are combined, synthesized, and reviewed for technical soundness and consistency with ISPE’s positions before being approved by the President and CEO of ISPE.

“Everybody who has a point to make and a position that's sensible and knowledgeable [is heard],” said Chris Potter, ISPE Technical Projects Advisor and a member of ISPE’s Regulatory Steering Council.

By contributing to the commenting process, added Minero, “you are really shaping the future of pharma.”

WHAT MAKES A GOOD COMMENT?

To write compelling comments, you have to put yourself in the shoes of the regulators. The people reading comments are typically the same people who wrote the draft document, so respect and sensitivity are key, said Christine Moore, Head of GxP Audit, Inspection, and Compliance of the pharmaceutical company Organon.

“They have ownership in it, and they think that what they wrote is absolutely clear because it was clear to them. So you need to be persuasive; you need to be polite; you need to be specific.” Moore speaks from experience, having spent years working on regulations and guidance at the US FDA before she moved to industry.

ISPE’s comments typically begin by praising what the draft document got right. People’s instinct is to focus on the problems, but it’s also valuable to offer encouragement and make it clear why you support particular passages.

Members who wish to comment should also consider at the outset what type of document they’re dealing with, said Potter. Regulations are about the big picture, so it’s not productive to ask for too much detail or obsess over each sentence. In guidance, details matter more.

Even with guidance, however, there’s a balance to be struck between including enough specifics for clarity versus making a document over-prescriptive. Moore said that while she was at the US FDA, she was inundated with requests for more examples, and these comments were often ignored.

Sometimes the solution is as simple as adding a “wiggle word” that leaves room for exceptions, said Moore. If the guidance could lead to problems in a few narrow situations, don’t ask the regulators to address each situation; just add a word like “usually” or “generally.”

Another common misstep is complaining that something isn’t clear without explaining why. If a passage could be interpreted in two different ways, said Moore, lay out the possible interpretations, and explain why one would be a problem. When possible, offer new phrasing that could solve the issue.

And, she added, it’s best to avoid phrasing comments as questions. Instead of asking “how does this apply to starting materials,” you can write “please include in the text how this applies to starting materials.”

Sometimes, the most insightful comments are about what’s missing. Commenters should consider the whole document and what it needs to accomplish, rather than focusing only on the words in front of them.

For example, in its recent comments on FDA-2024-D-4689 Draft Guidance: Considerations for the Use of Artificial Intelligence to Support Regulatory Decision-Making for Drug and Biological Products, ISPE suggested adding training requirements for people who develop, test, audit, and use AI-based systems, as well as requirements for ongoing evaluation to monitor the risk of model data drift.

“In this case, we suggested to be stricter than the regulators were at the beginning,” said Minero. “We thought, for the sake of patient health, it is exactly what we need to do.”

Often, of course, the problem is the opposite: A piece of guidance or regulation is too strict or impractical to implement. When raising those types of issues, Moore encourages ISPE members to leave behind the “gap assessment” mindset. People who work in industry are accustomed to assessing the gaps between their company’s current practices and a proposed change or goal. Large gaps create challenges for people at the company, but that’s not what regulators need to hear. They care about how it will affect patients.

“I can't tell you how many times I've seen people write comments to a document saying, “our company doesn't do it that way,’” said Moore. “The comments are for the regulators, not your company.”

Potter echoed the sentiment. “You can't just say you don't like it because it's extra work. You've got to find a good reason,” he said. For example, tell the regulators if the guidance would force manufacturing facilities to scale back in a way that could lead to drug shortages.

In the same vein, he said, it’s important to understand what the regulators were trying to achieve, and to suggest solutions with that in mind. “You’ve got to offer some alternative,” he said.

COMMENTS MAKE A DIFFERENCE

Thanks to commenting experts like Moore and Potter and the diverse skills and experience of its membership, ISPE has a reputation for delivering comments that matter. It has also earned credibility by offering scientific and technical guidance without political spin.

“It’s not a lobbying organization,” said Potter. “We are trusted because we haven't got that agenda.”

Regulators value ISPE’s input so highly that they sometimes request it, even on projects and documents that aren’t open for public comment. For example, in 2018, ISPE was one of only four organizations asked to comment on the Pharmaceutical Inspection Co-operation Scheme (PIC/S) data integrity guidance PI 041-1 Draft 3.

In addition to adding authority to members’ ideas, ISPE commenting also provides a way for members to influence regulatory documents anonymously, independent of their company’s comments or positions, said Moore.

“I might contribute comments through ISPE that might not show up in my company's comments, because they're my personal opinions,” she said. “By being able to bring your ideas in through ISPE, you can have your voice heard.”

Commenting can also be valuable on a personal level, helping industry members understand the challenges of crafting – and then complying with – regulation, said Minero.

Most importantly, commenting makes for better regulation, and that benefits everyone.

“Everybody has loved ones, friends or family, whose continued health and even survival is reliant on our products in the industry,” said Wakeham. “Industry and regulators need to be a partnership working together for the ultimate safety of the end patient.”

Find open commenting opportunities and view past ISPE comments.