Contract Research Organizations | How to Choose & Find CRO | Concern before selection of CRO | Pharmacovigilance Notes
Contract Research Organizations
Contract research organizations, otherwise known by the acronym CROs, are service organizations located all over the world that provide services to a wide variety of businesses in a broad spectrum of industries.
CROs range in size from small niche service providers to the large full (‘we do it all’) service CROs.
CROs provide services that exist within the domains of good laboratory practice (GLP), good manufacturing practice, and good clinical practice as well as outside the boundaries of such areas
Definition:
The International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, a 2015 Swiss NGO of pharmaceutical companies and others, defined a contract research organization (CRO), specifically pertaining to clinical trials services as “A person or an organization (commercial, academic, or other) contracted by the sponsor to perform one or more of a sponsor’s trial-related duties and functions.”
Need of CRO
To save the funds of Research
To save the Time for research
Work completed by specialized organization and specialized professionals
History of CRO
Contract Research organizations have been around for a long time. The oldest in the United States was Food and Drug Research Laboratories, which opened for business in the 1930s in suburban New Jersey and closed for business in the 1980s.
Starting around 1975, a number of different toxicology laboratories came into existence and after varying periods of time, went out of business. Some, but not all of these laboratories were
- Bioassay Systems,
- Tegaris,
- Bushy Run,
- Utah Biomedical
- Biotesting Laboratory,
- HTI, and
- Oread.
Over the years, especially recent years, in addition to closures, there have been a number of acquisitions and mergers of different laboratories.
Hazleton has evolved into Covance and Charles River has accumulated a number of smaller organizations all ultimately assembled under the ‘Charles River Laboratories’ name. All these activities are ultimately driven by the drive for the generation of top line revenue and the maximization of profit.
Various economic pressures have also forced some of these changes (mergers and closures) in the pharmaceutical contract research industry.
Services provided by CRO
Specific areas of expertise can include biology, chemistry, clinical science, pharmaceutics, and regulatory expertise.
Within the biology niche, offerings can include both the in vitro and the in vivo screening of test articles for lead identification and lead optimization as well as efficacy
modeling, genetic toxicology, animal toxicology, immunotoxicology, pharmacokinetics, and metabolism.
For chemistry services, one would expect to find synthesis and the scale-up synthesis of test articles, active pharmaceutical ingredient (API) manufacture, radiosynthesis, and analytical and bioanalytical method development and validation.
Clinical services would include the availability of actual Phase 0 and Phase I Centers, data and site management services along with the services of statisticians, and clinical research associates along with report writing services. These latter services are also typically available for studies conducted at Phase II/III sites.
Services within the discipline of pharmaceutics would include formulation development and drug product manufacture.
Finally, organizations that specialize in the area of regulatory services in addition to the provision of regulatory advice also offer compilation and writing for an Investigational New Drug Application (IND), New Drug Application (NDA), Investigational Device Exemption, 510(k), Premarket Approval, Common Technical Document, Drug Master File, and Annual Updates.
Critical areas of consideration in the selection of a CRO
- (1) dependability,
- (2) actual prior experience with the activity or specific study (do not be scared by being the first program of its type, but rather look to see if the proper systems and resources are in place to do the project properly),
- (3) training of personnel,
- (4) status and type of equipment required to perform the project,
- (5) cost of the project,
- (6) state of facilities,
- (7) regulatory history,
- (8) state of IT systems,
- (9) financial soundness,
- (10) physical location and accessibility,
- (11) references and reputation,
- (12) procedures in place to protect client confidentiality,
- (13) acceptability of study scheduling,
- (14) special considerations,
- (15) the wording and terms of the Master Services Agreement,
- (16) the format and detail of a study protocol,
- (17) company position on authorship,
- (18) the on-time report delivery record,
- (19) openness to inspections by the Sponsor
How to find CRO
- A variety of lists and advertisements exist in trade journals, professional journals, and books that can be extremely helpful.
- CROs usually attend scientific meetings, and so a great volume of information can be obtained by visitation and personal interaction at these functions.
- Professional colleagues are also a good source of information; however, be careful of potential bias, either positive or negative in these discussions. Follow through with your own investigation and make your own decisions.
How to Check The Accuracy of CRO
- A good place to start is to visit the Food and Drug Administration (FDA) website and look for copies of laboratory inspection reports that have been conducted by federal agencies and are available for free under the Freedom of Information Act.
- While some specific information may and probably will have been purged from the reports, they are still of great value with regard to laboratory operations and
systems. Since the inspection procedures used by the government are very consistent, these reports facilitate the comparison of different laboratories when evaluating the form and function of different systems. Keep in mind that effort must be made to put findings and citations in the proper perspective. - All points mentioned on an audit report are not necessarily of equal importance and severity, and indeed some may even be considered to be trivial in nature. When it comes to visits to the various laboratories, one may wish to perform actual visits or interviews themselves of the various CROs under consideration or work through an intermediary, such as a suitably qualified toxicology or safety assessment consultant
Top CRO of World by turnover
As of 2016, there was a 15.5% increase in R&D spending from 2015 to 2020. The list of Contract research organizations includes the following notable companies worldwide:
- Laboratory Corporation of America Holdings (Covance) ($14.00B revenue in 2020)
- IQVIA ($11.35B revenue in 2020)
- Pharmaceutical Product Development (PPD) ($4.68B revenues in 2020)
- Syneos Health ($4.41B revenue in 2020)
- ICON ($2.79B revenues in 2020)
- PAREXEL International Corporation ($2.44B revenues in 2017)
- Charles River Laboratories International Inc (CRL) ($2.92B revenues in 2020)
- Wuxi Apptec ($1.01B revenues in 2017)
- Medpace Holdings, Inc ($0.92B revenues in 2020)
- KCR
Market size and growth of CRO
In 2018 global CRO market stood at $38,396.4 mln. and is projected to reach $90,926.3 mln. by the end of 2026, exhibiting a CAGR of 11.4% in the forecast period.
Key factors attracting both US and European companies to CROs in these new countries include
- Significantly cheaper pricing,
- Fewer animal rights issues and concerns,
- A strategy to capture work from the large, growing economies in the new CRO host countries, and access to larger and new groups of subjects for clinical trials.
Approach with regard to the use of CROs in these new countries?
- First, perform extensive and thorough qualification audits.
- Second, spend the time to develop proper, detailed, specific, and effective standard operating procedures and protocols.
- Third, maximize on-site monitoring of critical phases of studies conducted at such facilities.
- Fourth, place work and conduct business with laboratories that have some documented track record of performing regulated studies and submitting reports to the FDA and European Medicines Agency (EMEA)
Some common problems might arise with new CRO
(1) changes in key study or organizational personnel;
(2) lack of clarity in lines of authority and signatory responsibilities;
(3) lack of adherence to and slippage in attainment of timed milestones;
(4) lack of regulatory compliance;
(5) failures in quality control procedures and/or quality assurance procedures;
(6) poor or inappropriate selection of proper technology to generate data;
(7) actual closure of the testing facility (a more common concern these days);
(8) acts of nature;
(9) miscommunication, ineffective communication, or stretching the truth;
(10) the use of silent or stealth subcontractors;
(11) the existence of potential conflict of interest alliances;
(12) overpromising and under-delivering, or in other words overly committing to too much work for the
available resources at hand; and
(13) simple extraneous events associated with the perpetration of errors.
Reference
Contract Research Organizations
(https://www.sciencedirect.com/science/article/pii/B9780123864543009659)