Table 2: Sequential stages of activities, their timelines, potential causes for delays, and recommendations to reduce delays in PET biodistribution studies.

ActivitiesApprox. time (months)Potential causes for delays Comments and recommendations for improvement in timelines

Stage I (all activities can be done simultaneously): time 1-2 months

Initial study discussion formulation of an outline research plan2 monthsPrevarication, and absence of key decision makersClear communication and clear goal setting by the respective team leaders

Confidentiality agreements completion1-2 monthsLegal issuesPreexistence of a master services agreements

Formation of study teams with clear definition of roles and responsibilities 1 monthOrganisational issues
Availability of experienced staff and agreement
Ensure inclusion of key staff, chemists, regulatory, clinical, biologists

Contract agreements 1-2 monthsDisagreements on pricing and intellectual property rightsEarly finance and legal involvement. Work with contract-based imaging services providers

Stage II  (all activities can be done simultaneously): time 4–7 months

Radiochemistry feasibility and production of radiolabelled NME (non-GMP or GMP)
Implementation of GMP radiochemistry (RC) and its validation
Preclinical dosimetry study
Animal toxicology studies
4–7 monthsRadiochemical method development issues
Issues with procurement of precursor (GMP or non-GMP)
Problems transferring from non-GMP to GMP settings
Selection of PET centre with good track record of developing and implementing radiopharmaceuticals for clinical use and management of drug maker expectations
Preferred approved suppliers
Duplication of equipment for straightforward transfer of methods, development of cassette based chemistry, good communication, and regular interactions
Agreement of clear milestones and associated timelines for “Go-No Go” decisions

Stage III (all activities can be done simultaneously): time 3–6 months

Preparation of IMPD dossier for submission to MHRA1 monthSubject to delays in GMP implementation Experienced personnel to complete CMC section

Identification of clinical collaborators
Initiation of contracts with hospital
3 monthsIdentification and selection of appropriate clinicians
Realistic assessment of recruiting potential
Initiate early in Stage III as can cause significant delays
Preferred clinicians, imaging centre-linked clinical units

Development of research study protocol2 monthsInternal hierarchical and regulatory approval

Preparation and submission of regulatory submission to the REC, MHRA, and ARSAC and to hospital R and D2 monthsCMC section completion due to RC implementation delays
Delays in getting a date for an REC meeting
Done via the common IRAS However, MHRA and ARSAC require additional information to that provided by IRAS

Obtaining regulatory approvals and study initiation2-3 monthsDelays if there are queries or need for modifications
Variable calibre of ethics committee to review such studies
Hospital R and D approval not time-bound
Submission to or designation of ethics committees to review such studies