{"id":4672,"date":"2025-07-06T21:37:57","date_gmt":"2025-07-07T03:37:57","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=4672"},"modified":"2025-07-06T22:16:07","modified_gmt":"2025-07-07T04:16:07","slug":"regulatory-interactions-1","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/07\/06\/4672\/regulatory-interactions-1\/","title":{"rendered":"REGULATORY INTERACTIONS \u00a0– 1"},"content":{"rendered":"

\"\"<\/a>It can feel like the mountain stage of the Tour de France\u2026<\/p>\n

A lot of effort goes into preparing for meetings with Regulators.\u00a0 There is also a lot we can learn at such meetings. Today we start a series of blogs detailing personal experiences and learnings, highlighting do\u2019s and don\u2019ts.<\/p>\n

We had a fair number of interactions with regulators in the US, Canada, Europe, and Asia presenting and defending global projects and country specific development plans, We also have experience with Briefing Books, Guidance development and responses to queries.<\/p>\n

Meetings with Regulators are usually stressful encounters as much is at stake, for your company and for your project.\u00a0 A team\u2019s ability to interact productively and skillfully will be put to the test (and scrutinized at the post-mortem).<\/p>\n

Companies invest considerable time and effort preparing for Agency interactions by assembling teams and coaching internal speakers and outside experts\/KOLs.\u00a0 This all requires a lot of planning and coordination.\u00a0 The outcome of an End-of-Phase 2 (EoP2) meeting can have major consequences for a program if the Regulators demand an extra study or a more complex pivotal trial. These delays cost time and effort; ultimately lost time is lost money.\u00a0 On average, the opportunity costs of each additional year spent in development are in the range of $300 mio \u2013 $400 mio.\u00a0 Such extra costs may sink or derail an entire program, as the company elders may decide to invest elsewhere.<\/p>\n

Occasionally we had Agency interactions dealing with unanticipated events.\u00a0 We once requested a meeting regarding a Phase 3 trial for which a change in primary endpoint was considered desirable based on newly published data.\u00a0 The company suggested changes that also included an added interim analysis and a new SAP.\u00a0 However, the Agency made it clear that any late stage changes to the originally agreed study plan would be risky and considered problematic.\u00a0 Reviewers would question the company\u2019s motivation and investigate whether the true reason was an unblinded data review.<\/p>\n

Other meetings dealt with emerging safety aspects during a trial or program. For example, several meetings were prompted by the FDA regarding quinolone safety.\u00a0 The topics were pediatric use, tendon and cartilage damage, effects on CNS, and, of course, QT prolongation. \u00a0When increases in BP and HR were noted by a partner company studying a CNS drug, these deviations from normal were considered to be minor.\u00a0 Regulators were informed and agreed with the interpretation and proposed monitoring plan.<\/p>\n

Post-approval, companies may be asked to evaluate safety signals identified in the AERS system.\u00a0 All of these become high-stake interactions.<\/p>\n

Then there are the more technical meetings.\u00a0 Regulators sometimes ask for company input on diverse topics like the role of data modelling, the use of adaptive study design, PK\/PD and its value for dose selection, or the appropriateness of certain animal tests.\u00a0 At times, industry or PhRMA is invited to comment on proposed changes to guidances.<\/p>\n

There are numerous Regulatory Service companies that can help prepare for important meetings like an FDA Advisory Board session.\u00a0 Having dealt with several such companies, we need to be realistic about what to expect.\u00a0 Those that specialize in Advisory Board presentations are usually very good with the technical aspects and logistics of such meetings.\u00a0 They also can be good coaches on the behavioral \u2018soft skills\u2019 and how to deal with challenges.\u00a0 Of course, they cannot be expected to be subject matter experts; it is their operational know-how that is most useful.\u00a0 These AdBoard prep teams have people with fast fingers and grandmaster-level skills with Powerpoint.\u00a0 This allows the project team to focus on the task at hand without being encumbered by slide production and other onerous but necessary chores; this is not a minor contribution.<\/p>\n

Of course, these presentations should never have promotional overtones.\u00a0 The in-house team, clinician consultants and subject matter experts are expected to stick to the data in the context of similar compounds.<\/p>\n

Interacting with regulatory authorities across the world teaches that \u2013 beyond the specifics – certain general themes emerge.\u00a0 When we present our data, they will be evaluated by Agencies with the rules in their jurisdiction, ie., within the \u00a0\u2018regulatory framework\u2019 of a country or region.\u00a0 Looking at the same data package, regulators in the US may have different views from their counterparts in Europe or Asia. \u00a0The same data presented by Lilly for Xigris\/drotrecogin resulted in different labeling from the FDA and EMA.\u00a0 We will give examples and try to explain why this is unlikely to change in the years ahead.\u00a0 Vive la difference!<\/p>\n

As you know, there was a rather disjointed regulatory \u2018world\u2019 out there before ICH was implemented, to the point that truly global pharmaceutical development only became feasible after ICH implementation.\u00a0 From acceptance of development philosophies for certain indications to the specifics of study design, especially endpoints and statistical approaches, ICH had a monumental impact on global drug development.\u00a0 While local or regional approval studies may still be required, we now have a much greater level of consensus among Agencies than before ICH.<\/p>\n

Agencies globally also exchange assessments and meeting minutes.\u00a0 Do not assume that a rejection by the FDA would not be known to EMA by the time you knock at their doors!<\/p>\n

It goes without saying that interactions with Regulators are never fun. So much can go wrong, and we are not at our best sometimes when in the witness stand,\u00a0 Even a well-rehearsed team can be caught off-guard by a reviewer\u2019s aggressive remark, an incompetent \u2018expert\u2019 speaking out of line, or a misunderstanding.\u00a0 Even today we have to deal with language barriers.\u00a0 Questions about obscure technical details may throw us off.\u00a0 The 60 minutes usually allotted to make our case can go by very slowly.\u00a0 Stay calm, listen and ask for clarification; engage your colleagues as needed.<\/p>\n

In the next blogs we will deal with common mistakes that can come back to haunt you.\u00a0 We will also dedicate a blog to ethnic and cultural sensitivity.\u00a0 Stay tuned as we continue our Tour de France of regulatory insights.<\/p>\n

ABBREVIATIONS
<\/strong>AERS\u00a0\u00a0\u00a0\u00a0\u00a0 Adverse Event Reporting System
EoP2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 End-of-Phase 2 (meeting)
ICH\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 International Council for Harmonisation of Technical Requirements for\u00a0 Pharmaceuticals for Human Use
PAC\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Post-approval commitment
PhRMA\u00a0\u00a0 Pharmaceutical Research and Manufacturing Association
SAP\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Statistical Analysis Plan
SOC\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Standard of Care<\/p>\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

It can feel like the mountain stage of the Tour de France\u2026 A lot of effort goes into preparing for meetings with Regulators.\u00a0 There is also a lot we can learn at such meetings. Today we start a series of blogs detailing personal experiences and learnings, highlighting do\u2019s and don\u2019ts. Continue reading REGULATORY INTERACTIONS \u00a0– 1<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":4676,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[140,3,18],"tags":[1271,2311,2320,2314,2319,625,5,1583,2312,631,93,2315,2054,2316,2317,2318,2310,2313,683],"class_list":["post-4672","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-interesting_facts","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-ansm","tag-bfarm","tag-cde","tag-drotrecogin-label","tag-ema","tag-fda","tag-harald-reinhart","tag-health-canada","tag-ich","tag-lilly","tag-nmpa","tag-pmda","tag-post-approval-commitment","tag-regional-regulatory-differences","tag-regulatory-meeting-preparation","tag-swissmedic","tag-tga","tag-xigris"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/HR_SLIDER-REGULATORY-1.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-1dm","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":4840,"url":"https:\/\/allphasepharma.com\/dir\/2025\/08\/05\/4840\/regulatory-interactions-2-the-kata-of-proper-behavior\/","url_meta":{"origin":4672,"position":0},"title":"REGULATORY INTERACTIONS\u00a0– 2 The “KATA” of Proper Behavior","author":"Harald","date":"August 5, 2025","format":false,"excerpt":"Language-related issues come up quite frequently.\u00a0 Most interactions with regulators are held in English, but not all of them.\u00a0 In China, it is Mandarin, and in Japan it is, well, Japanese.\u00a0 In Europe, it is mostly English, but French and German occasionally creeps into the dialogue.\u00a0 In China, even if\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/image.png?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":1234,"url":"https:\/\/allphasepharma.com\/dir\/2015\/01\/26\/1234\/why-some-did-not-make-it\/","url_meta":{"origin":4672,"position":1},"title":"Why Some Did Not Make It","author":"Harald","date":"January 26, 2015","format":false,"excerpt":"There are numerous reasons why drugs get stuck in development.\u00a0 Certainly, problems with efficacy or problems with safety are main reasons but there are many other \u2018derailers\u2019 as well.\u00a0 For instance regulatory issues or manufacturing, difficulties can stop a program.\u00a0 Occasionally, a suboptimal dose was chosen because of (1) incomplete\u2026","rel":"","context":"In "Did you know...?"","block_context":{"text":"Did you know...?","link":"https:\/\/allphasepharma.com\/dir\/category\/interesting_facts\/"},"img":{"alt_text":"toy train","src":"http:\/\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/01\/toy-train.jpe","width":350,"height":200},"classes":[]},{"id":1915,"url":"https:\/\/allphasepharma.com\/dir\/2015\/09\/07\/1915\/dalbavancin-approval-issues-a-case-of-much-ado-about-nothing\/","url_meta":{"origin":4672,"position":2},"title":"Dalbavancin Approval Issues: A Case of Much Ado About Nothing","author":"Harald","date":"September 7, 2015","format":false,"excerpt":"Dalbavancin has changed hands a few times in its development history, moving\u00a0from Lilly to Vicuron, then Pfizer and ultimately Durata. 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