Continued Complexity Of A High Profile CRO Data Integrity Case

While it is well recognized that any pharmaceutical company implicated with data integrity issues could have significant impact on its business and survivability, the impact from a similarly implicated CRO would be even greater as it could severely impact all sponsors’ pending and approved products. A case in point is Cetero/PRACS.

In 2010, FDA issued an untitled letter to Cetero, a leading (at the time) early-phase CRO, expressing significant concerns regarding the integrity of Bioequivalence Bioavailabilty (BEBA) data generated over a five-year period.  FDA’s Office of Scientific Investigations (OSI) inspections had uncovered a systemic practice of conducting “prep runs” using subject samples to pre-screen the Cetero Houston bioanalytical laboratory.  FDA/OSI found examples of using such practices to manipulate test results.  For instance, some subject samples were manipulated to produce more desirable results. FDA also observed the practice of falsifying time and date records. It is interesting to note that these practices of using “prep runs” and manipulating time and date records are very similar to recent FDA inspection observations of many overseas GMP analytical laboratories.  It has been observed that many of these GMP analytical laboratories manipulated time and date records and were also found to have engaged in the alleged practice of routinely conducting “trial injections” (or “prep runs”) using test samples to pre-screen samples. Incidents of potential data and sample manipulations including back-dating were also observed.

The subsequent FDA enforcement actions on Cetero created a tremendous regulatory burden on a large number of its current (at the time) and former sponsors, as they were required to either repeat the studies or perform an FDA mandated third-party e-data audit for each affected study in accordance with an FDA approved e-data audit plan, or face potential regulatory actions on their pending or approved/marketed products. To meet the very tight timeline imposed by the FDA, many pharmaceutical companies had no choice but to hire third-party consultants with qualifications acceptable to the FDA/OSI and expertise in auditing bioanalytical data to conduct the required audits.  Lachman Consultants was hired by a number of Cetero’s sponsors in support of these very labor intensive and highly specialized audits and (we are happy to say) successfully completed many audits for affected studies.

In 2012, prior to the completion of the FDA-mandated remediation/audit activities, Cetero filed for Chapter 11 bankruptcy, restructured and changed its name to PRACS.   PRACS continued the business relationship with the former Cetero sponsors and continued the FDA-mandated remediation/audit activities.  Despite these efforts, in March 2013, PRACS unexpectedly ceased all operations and filed for Chapter 7 bankruptcy.  All of its employees were laid off with only a few hours notice and all of its facilities (including all off-site storage study records, investigational drugs and subject specimens) were locked down by the Bankruptcy Court under the control of the Court-appointed trustee.

The sudden closure of PRACS created yet another dimension of complexity for a large number of former Cetero/PRACS sponsors. Former sponsors not only had the need to gain access to their recent study records, test articles and subject specimens in support of their pending filings but also needed to gain possession of their archived study records, which were stored in various off-site locations in support of their approved/marketed and research products that were (and still are) under the control of the Court-appointed trustee. Upon approval of the Bankruptcy Court, Lachman Consultants was retained by a group of former PRACS sponsors as the third-party independent consulting group working with the Court-appointed trustee to support an orderly and compliant sponsor property retrieval process. A Master Protocol was developed by Lachman Consultants to ensure that the retrieval process conforms to applicable laws and regulations and preserves the integrity of the retrieved property to support the regulatory review and inspection and/or sponsor certification processes that may be required. Communication with FDA/OSI was undertaken to obtain their input on the proposed retrieval process. In order to facilitate the retrieval process, Lachman Consultants retained former key PRACS QA, clinical and bioanalytical employees to work with Lachman Consultants’ in-house GCP/GLP/Bioanlaytical experts. Many former PRACS employees were also retained as contractors to support the very labor intensive process of retrieving the huge volume of sponsor property including hard copy and electronic clinical, bioanalytical and related GCP/GLP compliance records in a compliant manner.

The retrieval of sponsor property is complicated by virtue of the fact that many of the off-site archived records are not stored in a sponsor-specific manner. The records contained in a particular storage box could include more than one sponsor’s records and, as such, these storage boxes cannot be simply shipped to a sponsor without prior review and sorting. Lachman Consultants has been working with many sponsors to address and resolve these issues and has successfully sorted and retrieved many records for a large number of former PRACS sponsors.

The retrieval process was further complicated when the last former PRACS facility in Fargo, ND where most of the recent study records were located and from which Lachman Consultants was conducting the retrieval process, was sold to a third-party in late 2013. Legal arrangements had to be made with the new owner in order to allow Lachman Consultants to obtain access to the sponsor study records to be able to continue the retrieval process.  This sudden change of ownership created an additional financial and logistic burden for all sponsors participating in the retrieval process.

Four years have passed since Cetero received the untitled FDA letter and Lachman Consultants is still working with many former sponsors to facilitate the retrieval of their study records.  Nevertheless, the current process will soon come to an end as the bankruptcy case winds down.  The Court-appointed trustee has sent out notices to many former sponsors to inform them that their records will be deemed abandoned and destroyed if they are not claimed and to request appropriate timely actions from these sponsors. However, it should be noted that, due to the long history of Cetero/PRACS and many consolidations of pharmaceutical companies that have occurred over time, the sponsor list available to the trustee may not be as complete as one would desire. Lachman Consultants continues to receive new inquiries from various former sponsors regarding retrieval of their records. For one reason or another, these new sponsors either claimed that they have not been notified or they had not reacted to this situation in a timely manner. Lachman Consultants has been advising all sponsors that time is of the essence to find an acceptable pathway forward to avoid unexpected destruction or “contamination” of their records when the bankruptcy case is closed.

The issues observed at Cetero/PRACS are not unique and could potentially occur at any CRO. The alleged data integrity issues recently uncovered by FDA at many overseas generic pharmaceutical companies could also occur at overseas CROs. Based on publically available information, another potential data integrity case had emerged in July 2014. European regulators were asking pharmaceutical firms to submit information on products that were part of bioequivalence trials conducted at GVK Biosciences, a CRO based in India.  GVK was inspected and serious concerns were raised by the European regulators regarding good clinical practice compliance that could potentially impact data integrity, similar to the Cetero/PRACS case.

If your firm needs further information relative to the Cetero/PRACS matter or has concerns related to other CROs, please contact Jim Davidson, Ph.D., Vice President, Science and Technology at