Bioequivalence and Bioavailability Forum

Dear Prasant!

❝ Please let me know the Quantity of retention sample to be retained at the BA/BE center after completion of the trial.

Are you talking about (I) the drug products or (II) the bioanalysis samples?

I: Depending on the country’s regulation. Unused drug may either be destroyed, send back to the sponsor, or some samples may be retained. In any case records about the procedures followed have to kept.

US-FDA:
VI. RESPONSIBiLITIES IN VARIOUS STUDY SETTINGS
A.Studies Conducted at CROs, Universities, Hospitals, or Physicians’ Offices
The responsibilities of the testing facility are as follows:

• The clinical investigator or designee (such as the study coordinator or research pharmacist of the testing facility) should randomly select sufficient test article and reference standard to conduct the study from the supplies received from the sponsor and/or drug manufacturer, and retain the remaining study samples as study reserves.
  
• The testing facility or the pharmacy of the testing facility should retain the reserve samples.
  
• If the testing facility does not have adequate storage, or goes out of business, the reserve samples can be transferred to an independent third party with an adequate facility for storage under conditions consistent with product labeling.

Canada-HPB:
5.2 Regulations
C.05.012
(2) The sponsor shall maintain complete and accurate records to establish that the clinical trial is conducted in accordance with good clinical practices and these Regulations.
(3) The sponsor shall maintain complete and accurate records in respect of the use of a drug in a clinical trial, including:
[…]
e. records respecting the shipment, receipt, disposition, return and destruction of the drug;
(4) The sponsor shall maintain all records referred to in this Division for a period of 25 years.

EU-EMEA:
Article 11 (Quality control)
2. […] For investigational medicinal products, the sponsor shall ensure that the contract laboratory complies with the content of the request referred to in Article 9(2) of Directive 2001/20/EC, as accepted by the competent authority. When the products are imported from third countries, analytical control shall not be mandatory.
4. […] Samples of each batch of finished medicinal product shall be retained for at least one year after the expiry date.

India-CDSCO:
8. RETENTION OF BA/BE SAMPLES
All samples of test and reference drug products used in bioavailability / bioequivalence study should be retained by the organization carrying out the bioavailability / bioequivalence study for a period of three years after the conduct of the study or one year after the expiry of the drug, whichever is earlier. The study sponsor and/or drug manufacturer should provide to the testing facility batches of the test and reference drug products in such a manner that the reserve samples can be selected randomly. This is to ensure that the samples are in fact representative of the batches provided by the study sponsor and/or drug manufacturer and that they are retained in their original containers. Each reserve sample should consist of a quantity sufficient to carry out twice all the in-vitro and in-vivo tests required during bioavailability / bioequivalence study.
The reserve sample should be stored under conditions consistent with product labelling and in an area segregated from the area where testing is conducted and with access limited to authorized personnel.


II: IMHO no specific guidelines exist, but a commonly applied rule is:

• Keep all samples and ≥1 set of QC-samples for at least half a year or for the validated long-term stability period (whichever is longer) after acceptance of the analytical report by the sponsor.
  
• After this period update your long-term stability data, and talk to the sponsor about further storage or destruction of biosamples.
  
• Keep samples of at least one subject for an indefinite period of time, irrespective of the analyte’s stability (may be very helpful if an inspection takes place some years later).