A Clinical Hold (CH), whether complete or partial is an FDA order that halts the progress of an IND and can have a significant impact on the applicant’s bottom line.

Clinical hold orders are issued by the FDA for a variety of reasons explained in the Code of Federal Regulations title 21 Part 312 (21 CFR 312) and can pertain to one or more aspects of the IND including pre-clinical, clinical and chemistry, manufacturing and control (CMC) information.

At the pre-clinical level “insufficient information to assess patient risk” is a leading reason with “lack of pre-clinical safety data necessary for the support of the relevant clinical trial” topping the list. “Inadequate study design” is another reason with the “use of biologically irrelevant animal models” being a specific example.

Similarly at the clinical level, safety related deficiencies include “unanticipated toxicities” while patient population deficiencies refer mainly to “inappropriate eligibility/exclusion criteria”. Finally at the CMS level reasons include reagent, manufacturing and testing deficiencies.

Avoiding and addressing Clinical Hold situations

How can a sponsor avoid clinical hold situations or react to one once the FDA has sent the CH notification?

At the IND preparation stage the obvious answer is to aim for more complete information, better thought out and justified choices, more complete coverage of eventualities (like adverse event anticipation). Once a Clinical Hold letter has been received however, the ability to respond not only in a very concrete manner but also in a short amount of time becomes critical.

For example when a patient experiences an unanticipated adverse event, being able show that the patient's illness stems from a pre-existing condition rather than the new drug being tried, can prove critical for the sponsor.

How can Biovista help sponsors?

Biovista’s Drug Development and Regulation (DDR) service offers a range of solutions that help sponsors effectively deal with clinical hold situations. Patient population selection with appropriate inclusion/exclusion criteria, adverse event prediction and benefit/risk assessments are a few of the DDR service solutions that support drug development teams and decision makers.

Advantages of the DDR service include

1. Rapid reaction capability (down to a month) helps get the investigation back on track in very short timeframes
2. Breadth of coverage (ensures solid basis for recommendations) covering multiple non-obvious eventualities
3. Ability to offer biological plausibility reasoning for possible interpretations of adverse event occurrences during trials can help exonerate the drug being investigated
4. Significant time and money savings

To find out more about our Clinical Hold service please contact us.