When it comes to GCP sponsor inspections there are numerous agencies throughout the world that may review your organizational practices. There only a handful, however, that all companies are virtually guaranteed to be inspected by. The organizations referred to are the Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Medicines and Healthcare products Regulatory Agency (MHRA) and the Pharmaceuticals and Medical Devices Agency (PMDA) (which falls outside the scope of this article). The observations noted are firsthand experiences of the differences between agencies during inspections and will be reviewed by category.

Agenda

While the FDA will agree to a schedule for their visit they will not provide a breakdown of the topics they intend to review and discuss. These can be anticipated by reviewing the Bioresearch Monitoring Program (BIMO) manual in advance of the visit. The EMA/MHRA, on the other hand, will provide a detailed agenda of the topics they intend to review and discuss. It is important regardless of the agency however to understand that the schedule will often change and to be prepared to accommodate that.

Inspection Focus

FDA inspectors will spend some time reviewing general processes (e.g. related to safety reporting and Investigational Product handling), but their primary focus will be on study specific activities. The approach will generally be to follow the BIMO manual and to assess compliance on a given study. The EMA/MHRA while also focusing on study specifics in their trial master file (TMF) review will focus primarily on general processes in their Subject Matter Expert (SME) interviews.

Studies

While the FDA and EMA will inform you well in advance of the study or studies they are planning to inspect, the MHRA will often wait until two weeks prior to the inspection. Additionally they may choose unexpected studies. For example, while they might select an anticipated pivotal trial, they may also choose an extension study, a Phase I study or a study run by an organization your company has acquired or merged with. Therefore, it is advisable to be prepared for all possible scenarios.

Inspectors

Whereas the FDA is more prone to send individual inspectors, the EMA and MHRA are more likely to send a team of two-three inspectors. Because of this, companies will usually want to match the number of SMEs to the number of inspectors when meeting face-to-face for interviews.

Trial Master File

The TMF is one of the most significant points of difference between the FDA and the EMA/MHRA. While each agency will review the TMF, the approach they will take is very different. The FDA will generally perform a targeted review in order to confirm information related to various sections in the BIMO manual. Their inspectors may directly review the TMF or they may request a guided review. Additionally, while they want to see documents provided from the TMF during the inspection, they will accept copies from other systems.

How well do you really know your competitors?

Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.

View profiles in store

Company Profile – free sample

Thank you!

Your download email will arrive shortly

Not ready to buy yet? Download a free sample

We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form

By GlobalData

Submit

UK USA Afghanistan Åland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos Islands Colombia Comoros Congo Democratic Republic of the Congo Cook Islands Costa Rica Côte d"Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati North Korea South Korea Kuwait Kyrgyzstan Lao Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, The Former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Micronesia Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Réunion Romania Russian Federation Rwanda Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and The Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and The South Sandwich Islands Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates US Minor Outlying Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam British Virgin Islands US Virgin Islands Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Kosovo

Industry * Academia & Education Aerospace, Defense & Security Agriculture Asset Management Automotive Banking & Payments Chemicals Construction Consumer Foodservice Government, trade bodies and NGOs Health & Fitness Hospitals & Healthcare HR, Staffing & Recruitment Insurance Investment Banking Legal Services Management Consulting Marketing & Advertising Media & Publishing Medical Devices Mining Oil & Gas Packaging Pharmaceuticals Power & Utilities Private Equity Real Estate Retail Sport Technology Telecom Transportation & Logistics Travel, Tourism & Hospitality Venture Capital

Tick here to opt out of curated industry news, reports, and event updates from Clinical Trials Arena.

Submit and download

Visit our Privacy Policy for more information about our services, how we may use, process and share your personal data, including information of your rights in respect of your personal data and how you can unsubscribe from future marketing communications. Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address.

EMA/MHRA inspectors, on the other hand, will perform a thorough and fully comprehensive review of the TMF and will with rare exception plan to directly navigate through the TMF without assistance. The majority of the time spent during the inspection will usually be in TMF review. Importantly, the expectation from these agencies is that most study documents will be found directly within the TMF and will have been entered in a contemporaneous fashion. If a TMF is prepared for an EMA/MHRA inspection, it will likely be ready for any other major agency.

Study Gaps

Another key point of difference between the FDA and the EMA/MHRA is the approach to be taken in regards to important gaps in study performance. Should study gaps be identified by the FDA it is highly advisable to discuss the issues frankly and with a focus on corrective and preventative actions taken as a result. There is not an expectation however for sponsors to proactively point out gaps to the inspectors.  Furthermore, given their targeted TMF review, it is less likely that the FDA will identify issues via the TMF.

The EMA/MHRA, however, have different expectations when it comes to the proactive identification of gaps in study performance. Given the highly comprehensive TMF reviews that they conduct, they are far more likely to identify critical gaps in performance. Additionally, they will often request that sponsors be up front about issues they will find. When sponsors comply with this it will not only foster a more collaborative inspection but will often be the difference between a critical and a major finding.

Team Document Reviews

When it comes to critical study documents such as an Investigators’ Brochure, Study Protocol or Master Informed Consent form, the agencies have different expectations on evidence of team review. If an FDA inspector is provided with an SOP showing, which team members are involved in the creation and approval of the document along with their signatures, this will usually be sufficient. The EMA/MHRA, on the other hand, expect direct proof of this and in fact recommend utilizing such programs as Please Review which enable the filing of a single document that includes a full audit trail.

In summary, negative inspection findings can be highly consequential to any organization. It is therefore essential to be fully prepared well in advance. This can be accomplished by learning as much as possible about the differences between the key agencies and what they expect, look for and will cite your organization for in the absence of. By being prepared for these inspections you will not only avoid significant findings in the future but will ensure that you are running high quality trials that will optimally benefit patients.