Thank you everyone who attended the live webinar: ‘Bridging the gap: connecting evolving bioanalysis expertise to a rapidly changing global biopharma industry‘. Below are responses to the questions posed during the live event that we did not have time to answer. We hope this is a useful resource and thank our webinar attendees and our speaker, Dr Stephanie Pasas-Farmer (BioData Solutions/Accutest Laboratories) for her time.
1. Shouldn’t clinical method validation and sample bioanalysis meet Good Clinical Practices (GCPs)?
According to the FDA regulatory guidance, clinical method validation and sample bioanalysis (for both large and small molecules) are not covered under Good Clinical Practices (GCP). The FDA GCP, as it relates to samples taken from a clinical trial, focuses on the rights of the subject(s) within a trial: for example this would include topics such as informed consent and the privacy and rights of the individual being maintained. However, GCP does not discuss how methods are to be validated and how these validated methods are to be implemented. What GCP does cover is how this data is to be used and who should have access to the data for the clinical trials, which is typically outside the scope of the bioanalytical/bioanalysis groups generating the data.
Similarly, the FDA’s Good Laboratory Practice (GLP) only covers nonclinical sample analysis and does not technically include the validation that must be completed in order to complete the sample analysis. Also GLP does not mention clinical validation or sample analysis at all. This can become a tricky situation when trying to create a compliance statement at the beginning of a method validation plan or in a method validation report for both clinical and nonclinical methods, one cannot truly claim GLP for these activities because technically GLP does not include these activities. However all of these activities are done with GLP in mind, so most groups do use this terminology in one way or another. For example, I have seen the following wording: “In the spirit of GLP”, “GLP as a quality standard”, etc.
2. You talk about different acceptance criteria for large molecule analysis; in the same matter would you also expect different acceptance criteria when using HRMS versus regular MS/MS analysis too?
The FDA guidance is broken down into two sections, chromatographic assays and ligand binding assays. Due to this and the fact that HRMS is interfaced with a LC system, I would suggest the acceptance criteria that is typically used for LC-MS/MS (i.e. ±15% nominal, ±20% nominal for LLOQ).
3. Is it better to perform the validation of a bioanalytical method (e.g. biogenic amines – dopamine, serotonin etc. – in biological fluids) according to FDA or is ICH guideline still sufficient?
When considering what guidance to follow, one needs to consider where the drug is to be filed and what regulatory body shall review the data. Although the method validation and sample analysis procedures are mostly harmonized, there can be slight differences in the requirements. For example, the US FDA does not consider method validation part of GLP activities so technically QA does not need to be involved in data review for the validation. However, for the EMA the method validation does fall under GLP and therefore QA must be involved and an in process audit must occur. Therefore, prior to method validation, the bioanalytical team should consider where this data will be submitted in order to meet the requirements. If more than one country is targeted for approval, what I have seen company’s do is to aim for the highest level of requirements to make sure the program meets all necessary requirements.
4. How can we cope with the patent for the analytical method with generic peptides of IgG by Genentech?
I would like to start this answer with the disclaimer that I am not an attorney. However, I did confirm my response with someone who is an Intellectual Property (IP) attorney. In order for a patent to be upheld for any actions to be considered infringing upon this patent’s IP, ALL the patents claims must be involved in the infringement and not just sections of the claims or individual claims. The patent being referenced is specific for the ADC being developed at Genentech even listing specific linkage chemistry. So the possibility of a method being exactly the same in all the claims of this patent are unlikely but should be considered by legal counsel.
The webinar is available here – Bridging the gap: connecting evolving bioanalysis expertise to a rapidly changing global biopharma industry.