Preamble
The loss of investigational products (IP) during a clinical trial severely influences the clinical trial’s integrity, participant safety, and regulatory compliance. When the absence of IPs is noticed during a clinical study, implementing the necessary measures by Sponsors in a timely manner is of great importance.
1. Determining the Characteristics of missing products
Understanding the nature of missing products is crucial on deciding the further steps. Some products used in a clinical trial are subject to license such as Investigational Medicinal Products (IMPs) some are not, such as Sterile Water for Injection (SWFIs).
2. What are the risks concerning the sale and consumption of the unlicensed substances?
During the criminal investigation phase, the Public Prosecutor's Office will first and foremost seek the testimony of the Hospital Management, Physicians responsible for the Clinical Research, Healthcare Professionals and Clinical Research Associates. Subsequently, it is possible that the Sponsor Company officials, Legal Representative and Company Managers may testify.
The Prosecutor's Office may decide in two different ways. 1- Decision of non-prosecution 2- Issuing an indictment
If a Decision of non-prosecution is issued, no criminal case is commenced before Criminal Courts.
If an indictment is issued, the indictment is sent to the Criminal Court and if the Criminal Judge accepts the indictment, a criminal case is started, and criminal trials are held. In criminal proceedings, the Court is not bound by the content of the indictment and has the authority to expand the investigation and collect new evidence.
The sponsor is exposed to investigation risks in the following framework of crime classifications:
Crime Classification: Pursuant to Article 186 of the Turkish Criminal Code one who sells, supplies, or possesses tainted medicines in such a way as to endanger the human life and health shall be sentenced to imprisonment from one year to five years and a judicial fine up to one thousand five hundred days. If this crime is committed within the scope of the exercise of a profession carried out on the basis of official permission, the penalty to be imposed shall be increased by one third.
Crime Classification: Pursuant to Article 187 of the Turkish Criminal Code, a person who produces or sells medicines in a way to endanger the human life and health shall be sentenced to imprisonment from one year to five years and to a judicial fine. If this crime is committed by a physician or a pharmacist or within the scope of the exercise of a profession carried out on the basis of official authorization, the penalty to be imposed shall be increased by one third.
3. Proposed way of action to mitigate the risks for the Sponsor:
There is a certain risk that an investigation can be initiated against the sponsor in case a third party is harmed by the substance. Sponsor can minimize the risk of such investigation by filing a criminal complaint.
Since this crime is related to production or sale, Sponsor needs to file a criminal complaint to prove that the stolen product was not provided to someone else by Sponsor.
4. Procedure to be followed:The stolen substances should be reported to the prosecutor’s office on the following grounds:
Aggravated Theft: Pursuant to Article 142/para 2-(h) of the Turkish Criminal Code. In case the offence of theft is committed with respect to the property which is left in a place accessible to everyone but locked or kept in a building or its annexes, imprisonment from five years to ten years.
Crime Classification. Article 19 of Law on Pharmaceutical and Medical Preparations: Those who manufacture preparations without a license or intentionally sell, offer for sale or cause to be sold preparations so manufactured shall be sentenced to imprisonment from one year to five years. The penalty shall be increased by one third if it is found that these preparations do not possess the therapeutic qualities attributed to them or are manufactured in such a way as to reduce or lose these qualities or are manufactured from impure substances. Those who sell, market or advertise any product with the declaration that it diagnoses or treats diseases, although it is not a preparation, shall be sentenced to imprisonment from one year to five years.
5. Administrative Reporting Obligations
Traceability, storage, return and disposal of research products. Article 37 of Regulation on Clinical Trials of Medicinal Products for Human Use:
Investigational products and investigational medicinal products for human use must be monitored, stored, returned and/or destroyed in accordance with good distribution practices. After the manufacture or import of the investigational product, the sponsor shall be responsible for the storage, distribution and delivery of the investigational product to the research center in accordance with the characteristics of the product, the implementation of procedures and instructions for the maintenance of these conditions in the research center or the confirmation of their existence in relevant places, the collection and return of unused products from the research center or their proper disposal and keeping records of this whole process.
In the disposal of research products, the provisions specified in the Waste Management Regulation published in the Official Gazette dated 2/4/2015 and numbered 29314 and the provisions of other relevant legislation shall apply. Receipt, storage, distribution of the investigational products in accordance with the written request or research protocol, stock control, procedures to be performed on the surplus and keeping records of them are under the responsibility of the principal investigator in each center where the research is conducted. It is essential that the principal investigator assigns a clinical trial pharmacist for these procedures. However, in studies where a clinical trial pharmacist cannot be assigned, the responsible investigator is obliged to take the necessary measures regarding the work and transactions of the products.
Reporting serious violations. Article 38 of Regulation on Clinical Trials of Medicinal Products for Human Use:
Any violation of the provisions of this Regulation and the approved research protocol affecting the safety and rights of the subjects or the reliability and quality of the data obtained in the clinical trial shall be notified to the ethics committee and the Agency by the sponsor within seven days at the latest as of the realization of this violation.
Other notification obligations related to patients safety. Article 39 of Regulation on Clinical Trials of Medicinal Products for Human Use:
(1) The sponsor shall notify the ethics committee and the Institution of all unexpected events affecting the benefit and risk balance of the clinical trial. This notification should be made as soon as possible, but no later than fifteen days from the date the sponsor becomes aware of this event.
(2) The sponsor shall notify the ethics committee and the Agency of all audit reports related to the clinical trial conducted in our country by the competent authorities of other countries and the translation of these reports. This notification shall be made within thirty days at the latest from the date the report is sent to the sponsor.
Notification Obligation
As explained in detail in the relevant legislation section above, the sponsor, the legal representative of the sponsor, the principal investigator or the investigator has the obligation to make notification to Ministry, Agency or the University Management, Ethic Board and the District Attorney’s office.
6. Emergency safety measures. Pursuant to Article 40 of Regulation on Clinical Trials of Medicinal Products for Human Use:
The sponsor, principal investigator or investigator shall take the necessary emergency safety measures to protect the subjects against these dangers in case a new situation that may affect subject safety arises during the conduct of the research or related to the development of the investigational product. The principal investigator or sponsor shall notify the ethics committee and the Institution about this new situation and the measures taken within seven days at the latest from the date the measures are taken. Otherwise, the Agency will stop the research.
We assume that Hospital Administration and Principal Investigator took necessary measures after theft incidence. We need further information or documents proving that Hospital Administration and Principal Investigator took necessary measures.
Administrative sanctions. Article 67 of Regulation on Clinical Trials of Medicinal Products for Human Use: The provisions of the Turkish Criminal Code other relevant legislation shall apply to those who act and operate contrary to the provisions of this Regulation, depending on the nature of their acts. Pursuant to the article, negligent behavior may be evaluated according to the characteristics of each case and punished according to the Turkish Penal Code.
7. Supreme Court Jurisprudence Concerning the Matter
Court of Cassation Decision - 2nd CD, E. 2019/1455 K. 2019/12733 T. 10.7.2019 While the defendant ... should be sentenced pursuant to Article 142/2-h of the Turkish Penal Code No. 5237 due to his act of stealing the medicines subject to the crime from the warehouse of the health center where he worked in September, November 2014 and January 2015, a sentence should be established pursuant to Article 142/1-a of the same numbered Law,
Since the appeals of the defendant ... defense counsel and the participant's attorney were deemed appropriate in this respect, it was unanimously decided on 10/07/2019 to REVERSE the verdict contrary to the request for this reason.
8. Civil law aspects regarding the pecuniary and non-pecuniary damages
It is reasonably unlikely that there will be any claims against the Sponsor under civil law aspects.
In the event that there are people who have suffered bodily harm due to the stolen IMPs, those who have intent (those who stole the IMPs - those who made the IMPs available - those who sold the IMPs, etc.) and those who are negligent (hospital management - clinical research responsible physician - clinical research healthcare professionals - clinical research experts - sponsor company and its legal representatives, etc.) may be held liable, taking into account the rate and severity of negligence. However, in this case, it must be proved that the bodily harm caused using the stolen IMPs directly, that the bodily harm caused a material damage (treatment costs, deprived earnings, compensation for deprivation of support, etc.), that the other party is at fault, and that there is an appropriate causal link between this fault and the damages incurred.
The Turkish legal system has regulated the strict liability of the administration and those who have suffered damages can also claim compensation based on the strict liability of the administration by filing an administrative lawsuit against the hospital management, the municipality, the Ministry of Health. In this case, there is no need to prove the negligence and fault. The occurrence of the damage is sufficient to claim compensation from the administration.
Conclusion
The sponsor, the legal representatives of the sponsor, the principal investigator or the investigator has the obligation to make notification to Ministry, Agency or the University Management, Ethic Board and the District Attorney’s office and other relevant authorities.
The sponsor and sponsor’s legal representatives should take the following actions to mitigate the risk of exposure to a sanction or legal proceedings:
- Submit the criminal complaint petition to District Attorney’s Office
- Submit the notification petition to Ethic Boards, University Management and Ministry of Health
Author: Att. Ugur Karacabey