IMP/Placebo Sourcing, Release, Storage and Reconciliation. Ms
Caroline Whiriskey Research Pharmacist, HRB Clinical Research
Facility Galway.
Slide 2
Sourcing of IMP/Placebo A sponsor responsibility Sourcing of
product(s) of acceptable quality Blinding / production of placebo
Labelling Quality and stability assessments Documentation
Slide 3
Sourcing of IMP/Placebo Quality Required amount of correct
drug, within acceptable limits No harmful excipients Fit for the
purpose of the trail Sufficient stability for duration of trial
Documentation to prove this Acceptable to participants See EMEA
CHMP: Guideline on the requirements to the chemical and
pharmaceutical quality documentation concerning investigational
medicinal products in clinical trials (2006)
Slide 4
Sourcing of IMP/Placebo Quality
Slide 5
Sourcing of IMP/Placebo Blinding Over-encapsulation Manufacture
of placebo Opaque covering for infusion / syringe Adverse effects
may unblind the participants James Lind 20th of May 1747
Slide 6
Sourcing of IMP/Placebo Labelling EudraLex, Volume 4: EU
Guidelines to Good Manufacturing Practice Medicinal Products for
Human and Veterinary Use: Annex 13 Investigational Medicinal
Products Labels should include: a) name of the sponsor; b)
pharmaceutical dosage form, route of administration, quantity of
dosage units (and name/identifier of the product and
strength/potency in case of open trial); c) the batch and/or code
number to identify the contents and packaging operation; d) the
trial subject identification number, where applicable; e)
directions for use; f) for clinical trial use only; g) the name of
the investigator (if not included as a code in the trial reference
code); h) a trial reference code allowing identification of the
trial site and investigator; i) the storage conditions; j) the
period of use (use-by date, expiry date or re-test date as
applicable), in month/year); k) keep out of reach of children
Slide 7
Sourcing of IMP/Placebo Documentation Application to the HPRA
must include: Investigational Medicinal Product Dossier (IMPD)/
Simplified IMPD (incl. Section 2.1 Pharmaceutical information,
Section 2.2 Pre- Clinical information, Section 2.3 Clinical
Information) for all IMP and for placebo a) Summary of Product
Characteristics (SmPC) for products with marketing authorisation in
the Community Investigators Brochure (IB) Examples of
labelling
Slide 8
QP Release A statement by a Qualified Person confirming that
the product has been manufactured to the standards which are
appropriate for the product and the way the product is intended to
be used. Required for all IMP. IMP sourced outside of the EU must
also be released by an EU QP before it can be sent to
investigational sites The first step of the procedure, QP
Certification ensures that the product has been manufactured in
accordance with the requirements of EU Good Manufacturing Practice
(GMP). The second step is the release of the IMPs by the Clinical
Trial Sponsor, which confirms fulfilment of the requirements of
Article 9 of the 9 of the EU directive 2001/20/EC (e.g.
approval/favourable opinion from IRB/IEC and regulatory
authority(ies))
Slide 9
Storage: In transit Transit storage is the responsibility of
the trial sponsor Depending on stability of IMP, distance
travelled, climatic conditions, may require transport in a
temperature-controlled shipper, +/- inclusion of a data logger to
demonstrate transit temperatures Responsibility of the investigator
to follow sponsor procedures for assessment of transit
conditions
Slide 10
Storage at site Secure location locked room or locked cabinet.
Appropriate temperature: Ambient 15-25 C or 15-30 C Refrigerated
2-8 C Protection from light may be needed Humidity may be an issue
in some climates. Monitoring, to verify that IMP was stored
appropriately at all times Report temperature excursions ASAP Alarm
system See HPRA Guide to Control and Monitoring of Storage and
Transportation Temperature Conditions for Medicinal Products and
Active Substances. (2011 )
Slide 11
Storage temperature mapping All rooms where trial drugs are
stored are temperature mapped before IMP is stored in them. All
fridges and freezers are temperature mapped before initial use.
(full and empty) Temperature loggers are placed in expected hot and
cold areas. (e.g windows,doors, near air conditioning units)
Initially carried out summer and winter for three years.
Slide 12
Storage temperature mapping
Slide 13
Storage: Fridges and freezers Fit for purpose Calibration prior
to use Temp mapped Do not over fill IMP storage only Ongoing
performance qualification Annual preventative maintenance and
calibration.
Slide 14
Storage: temperature loggers Annual calibration Three point
calibration over the range its being used at. Alarm logger and
monitoring logger are separate.
Slide 15
Storage: temperature loggers
Slide 16
Reconciliation: ICH GCP 4.6.3 The investigator/institution
and/or a pharmacist or other appropriate individual, who is
designated by the investigator/institution, should maintain records
of the product's delivery to the trial site, the inventory at the
site, the use by each subject, and the return to the sponsor or
alternative disposition of unused product(s). These records should
include dates, quantities, batch/serial numbers, expiration dates
(if applicable), and the unique code numbers assigned to the
investigational product(s) and trial subjects. Investigators should
maintain records that document adequately that the subjects were
provided the doses specified by the protocol and reconcile all
investigational product(s) received from the sponsor.
Slide 17
Reconciliation: Accountability logs
Slide 18
Standard Operating Procedures
Slide 19
Some useful documents HPRA guide to clinical trial
applications: v8 Aug 2014 European Communities (Clinical Trials on
Medicinal Products for Human Use) Regulations, 2004, SI No 190 of
2004 and amendments Eudralex, Volume 10: Guidance Documents
Applying to Clinical Trials, Questions and Answers EudraLex, Volume
4: EU Guidelines to Good Manufacturing Practice Medicinal Products
for Human and Veterinary Use Annex 13 Investigational Medicinal
Products IMB (HPRA) Guide to control and monitoring of storage and
transportation temperature conditions for medicinal products and
active substances (Oct 2011) EMEA CHMP: Guideline on the
requirements to the chemical and pharmaceutical quality
documentation concerning investigational medicinal products in
clinical trials (2006)