A well-conceived and executed clinical radiolabelled ADME program will provide you with a detailed assessment of the total fate (mass balance, route and rate of excretion, tissue distribution, metabolic pathways, and identity and quantity of metabolites) of your drug candidate to support regulatory submissions. This presentation explains in 10 steps how we conduct a Human Mass Balance Study at QPS.

1. Human Mass Balance Study
In 10 steps
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2. HMB Study at QPS
Reasons why our Clients recommend performing a HMB Study at QPS
QPS has extensive experience and expertise with the conduct of human mass balance studies
(references will be provided upon request).
The favorable regulatory environment in the Netherlands makes conducting human mass balance
studies at QPS an excellent choice.
The option of using QPS also as a preferred provider for the necessary preclinical radiolabeled study
package (i.e. tissue distribution study in rats using quantitative whole-body autoradiography, dosimetry
calculation, mass balance / excretion study in rats, and metabolite profiling, identification, and radio-quantitation
study) enables QPS to transfer the knowledge obtained from preclinical studies smoothly to
the human mass balance study in the Netherlands.
Smooth knowledge transfer from preclinical to clinical becomes particularly important when
metabolism pathways are complex and ensuring sample integrity becomes critical.
In addition, sponsors can take advantage of the fact that QPS uses a by QPS qualified and state of
the art radiopharmaceutical facility (Selcia, UK) with a governmental Manufacturer’s/GMP license
for the (individual) preparation of 14C-labeled IMPs. Because of these outstanding radiopharmaceutical
facilities, the availability of only the 14C-labeled drug substance is sufficient to carry out human mass
balance studies at QPS.
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3. HMB Study at QPS
Abbreviations
EC = Ethics Committee
CA = Competent Authority
CPU = Clinical Pharmacology Unit
CTP = Clinical Trial Protocol
IB = Investigator’s Brochure
IMP = Investigational Medicinal Product
IMPD = Investigational Medical Product Dossier
ICF = Informed Consent Form
PI = Principal Investigator
UMCG = University Medical Center Groningen
QP = Qualified Person
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4. HMB Study at QPS
In 10 Steps
Step 1: Ethics Committee & Competent Authority Submission
Step 2: Receipt and Release of 14C-labeled IMP
Step 3: Individual Drug Preparation of 14C-labeled IMP
Step 4: Transport and Drug Administration of 14C-labeled IMP
Step 5: Collection, Sample Processing and Transport of blood and Human Excreta
Step 6: Return and Destruction of 14C-labeled IMP
Step 7: Measurement of the 14C-Radioactivity in blood and Human Excreta
Step 8 Follow up of Measurement of the 14C-Radioactivity in Human Excreta
Step 9: Determination of the total 14C-Radioactivity Recovery Rate
Step 10: Disposal of 14C-labeled Human Excreta
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5. HMB Study at QPS
Step 1 – Ethics Committee & Competent Authority Submission
The application process for a radioactive phase I trial in the Netherlands is
essentially the same as for any other non-radioactive phase I trial
QPS CPU and Isotope lab are located in the same building and have a
permanent license to work with 14C, 3H and other isotopes
Written EC and CA approval is routinely obtained within 14 days after
submission of the Clinical Trial Application (CTA).
Submission documents as part of the Clinical Trial Application are:
Clinical Trial Protocol (CTP)
Investigator’s Brochure (IB)
Investigational Medical Product Dossier (IMPD)
Informed Consent Form (ICF)
Human Dosimetry Calculation which is done by QPS DMPK group
If required, all documents can be written by QPS
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6. HMB Study at QPS
Step 2 - Receipt and Release of 14C-labeled IMP
Radiopharmacy is located at the premises of the University Medical
Center Groningen. QPS CPU is located at the same premises at a distance
of approximately 200 meters.
QPS has a permanent contract with the Radiopharmacy
14C-labeled IMP is sent from the Sponsor or UK facility (Selcia) to the
Radiopharmacy
14C-labeled IMP is placed in quarantine at the Radiopharmacy until
release by QP (QPS QP).
14C-labeled IMP is entered in IBC-606 (fully automated & validated
Isotope Book Keeping System) of the Radiopharmacy.
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7. HMB Study at QPS
Step 3 – Individual Drug Preparation of 14C-labeled IMP
Per study subject drug preparation of 14C-labeled study medication is
done by the UMCG Radiopharmacist and the QPS Pharmacist.
Individual Drug Preparation Forms are prepared by the Clinical Trial
Pharmacy of QPS – documents are reviewed by the Radiopharmacy and
the Sponsor.
Label specifications are prepared according to GMP Annex 13 by the
Clinical Trial Pharmacy – documents are reviewed by the Radiopharmacy
and Sponsor.
Labels are printed (without batch number) by the Clinical Trial Pharmacy.
Unique batch numbers will be added in handwriting on the labels during
each individual drug preparation.
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8. HMB Study at QPS
Step 4 – Transport and Drug Administration of 14C-labeled IMP
14C-labeled study medication, prepared on a per subject basis, is picked up
from the Radiopharmacy and transported in a closed Perspex transport box
to QPS’s CPU (i.e. the place where drug administration takes place) by
Clinical Trial Pharmacy personnel.
Administration of the 14C-labeled study medication is always done in the
presence of the Authorized User and the PI or a designated Research
Physician.
Circumstances are essentially the same as for any other non-radioactive
phase I trial.
Additional hygienic measures are used to prevent radioactive
contamination of the CPU.
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9. HMB Study at QPS
Step 5 – Collection, Sample Processing and Transport of Radioactive Human Excreta
All necessary steps to ensure sample integrity (based on experience obtained from preclinical
studies) will be taken during sample collection, sample processing, storage, and shipping to
either QPS Isotope laboratory for radioactivity counting or DMPK for metabolic profiling.
Selection of samples for metabolic profiling are done by DMPK based on radioactivity levels per
sample
Collection of blood, urine, feces and expired air takes place in the CPU.
Processing of collected blood, urine, expired air and feces samples (i.e. homogenization and
aliquoting) takes place in the dedicated Isotope laboratory within the CPU
Volunteers are discharged from the clinic after at least 85 % (or more if the study protocol
requires to do so) of the total dose of radioactivity has been recovered in the excreta from the
volunteer.
Radioactive human excreta and/or aliquots, not needed for radioactivity counting, remain stored
in the CPU Isotope laboratory until shipment or destruction.
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10. HMB Study at QPS
Step 6 - Return and/or Destruction of 14C-labeled IMP
Returned/(partially) used 14C-labeled study medication is picked up from
the CPU (i.e. the place where drug administration takes place) and
transported in a closed Perspex box back to the Radiopharmacy by
Clinical Trial Pharmacy personnel.
Returned/(partially) used 14C-labeled study medication, if any, is stored
in a closed Perspex box in a locked cabinet in the Radiopharmacy until
approval for destruction has been received from the Sponsor.
Returned /(partially) used 14C-labeled study medication is considered
and handled as radioactive waste for which the Dutch guidance on
radioactive health and safety applies.
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11. HMB Study at QPS
Step 7 – Measurement of the 14C-Radioactivity in Human Excreta
After samples have been processed in the CPU, all necessary further
sample preparations prior to the actual measurement of 14C-radioactivity
are done by laboratory technicians from QPS own Isotope laboratory who
are GLP trained. They work in accordance with the particular Assays
Instruction(s) as required by the Bioanalytical Protocol of the concerned
study.
The measurement of 14C-radioactivity in human study samples is
performed on a beta-counter (Tricarb 2500) in the same Isotope
laboratory.
Measurements include so called “quick counts” to verify subject’s
discharge criteria from the CPU as well as all counting for the entire mass
balance determination
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12. HMB Study at QPS
Step 8 – Follow up of Measurement of the 14C-Radioactivity in Human
Excreta
Results of radioactivity counting are evaluated by our own DMPK group.
They will select samples from the appropriate matrixes for metabolite
identification/profiling
Selected samples will be shipped from the Isotope laboratory
Results are described in analytical reports whereas the appropriate PK
evaluations will be carried out and reported by our PK group
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13. HMB Study at QPS
Step 9 – Determination of the total 14C-Radioactivity Recovery Rate
Determination of the total 14C-radioactivity recovery rate is done by the
Statistics Department of QPS using validated excel sheets.
The total recovery rate from urine, feces and expired air samples will be
calculated during the last 24-hour interval of hospitalization on the basis
of quick count determinations. This percentage of 14C-radioactivity
recovery will be used as the discharge criterion for the volunteer in the
clinic.
The 14C-radioactivity recovery from all human excreta at all sampling
times and intervals will be documented in a validated excel sheet.
PK on total radioactivity will be calculated by QPS Pharmacokineticist
Results will be reported in a Clinical Study Report
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14. HMB Study at QPS
Step 10 – Disposal of Radioactive Human Excreta
All radioactive human excreta collected during mass balance
studies will be treated as radioactive waste and handled
according to the Dutch guidance on radioactive health and
safety.
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15. HMB Study at QPS
Campus of the University Medical Center Groningen
Clinical Pharmacology Unit
Isotope Laboratory
Radiopharmacy
Clinical Trial Pharmacy
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16. HMB Study at QPS
Functions Involved – Roles & Responsibilities
Functions Physical Location &
Affiliation
Roles & Responsibilities
Synthesis Laboratory Selcia, UK Synthesis of radiolabeled IMP, GMP quality
Radiopharmacy UMCG Radiopharmacy Receipt and Release of 14C-labeled IMP
Individual Drug Preparation of 14C-labeled IMP
Return and/or Destruction of 14C-labeled IMP
Clinical Trial Pharmacy QPS Clinical Trial Pharmacy Transport of 14C-labeled IMP
Individual Drug Preparation Forms
Label Specifications according to GMP Annex 13
Clinical Pharmacology Unit QPS Clinical Pharmacology Unit Drug Administration of 14C-labeled IMP
Sample Collection and Processing of Radioactive
Human Excreta (blood, urine, feces and expired air)
Isotope Laboratory QPS Isotope Laboratory Processing of Radioactive Human Excreta
Sample preparation and actual radioactivity
counting
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17. HMB Study at QPS
Functions Involved – Roles & Responsibilities (cont.)
Functions Physical Location &
Affiliation
Roles & Responsibilities
DMPK QPS DMPK Sample selection for metabolic profiling
Metabolic profiling and reporting of results
PK QPS PK Pharmacokinetic evaluation and reporting on
parent compound and metabolites, if applicable
Statistics QPS Biometrics Department Determination of the total 14C-Radioactivity
Recovery Rate
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18. Contact
Corporate Office
Delaware Technology Park
3 Innovation Way, Suite 240
Newark, DE 19711
info@qps.com
Tel: + 1 302 369 5601
www.qps.com
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