The document discusses outsourcing bioavailability (BA) and bioequivalence (BE) studies to contract research organizations (CROs). Outsourcing such studies is common for smaller pharmaceutical companies and generic drug companies that lack internal clinical and bioanalytical capabilities. When selecting a CRO, companies should qualify the CRO's clinical, bioanalytical, and pharmacokinetic capabilities to ensure compliance with good practices. The document provides details on evaluating a CRO's facilities, personnel, validation procedures, and ability to coordinate different stages of BA and BE studies.

1. Outsourcing BA & BE
to CRO
By
Kushal Saha, M Pharm, Pharmaceutics, MPH/10008/19

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DEFINITIONS:
What is Outsourcing?
Outsourcing is the business practice of hiring a party outside a company to perform services and
create goods that traditionally were performed in-house by the company's own employees and
staff.
Contract research organization (CRO) is an entity that extends support to pharmaceutical,
biotechnology and medical devices industry in the form of research services outsourced on a
contract basis.
Bioavailability: Measurement of the amount and rate at which the drug from
administered dosage form, reaches the systemic circulation and becomes available
at the site of action.
Bioequivalence: It is a relative term which denotes that the drug
substance in two or more identical dosage form, reaches the
systemic circulation at the same relative rate and to the same
relative extent i.e.; their plasma concentration-time profiles will be
identical without significant statistical differences.

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• Outsourcing was first recognized as a business strategy in 1989 and
became an integral part of international business economics.
• Outsourcing is generally done to reduce the costs and improving the
efficient resources within a company. Example of outsourcing is
bioavailability, bioequivalence, R & D department etc.
• A CRO may offer such services like: Biopharmaceutical development, Clinical & preclinical
research, Clinical trial, Pharmacovigilance, Biological assay development.
GOAL
• Contract research organization(CRO) provides much needed service to the
pharmaceutical sector. Full service CROs offer a comprehensive selection of
capabilities, while smaller “niche’’ CROs may focus on a narrow segment of
services (clinical or analytical only).
• All of these organization fulfill a need in that they provide the services
necessary for the approval of new clinical entities or generic drug products. A
sampling of these services is included.

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Reasons of outsourcing
Many of the large pharmaceutical companies have in- house capacity but some of which lack
of in-house capacity, skill deficiency and cost control. For example many often have their own
clinical and bio analytical units that provide full support for phase 1 studies. However, even
these internal resources can become saturated due to the drive to develop more compounds in
shorter time interval.
Unlike their larger counter parts, the smaller companies, virtual firms and generic
companies do not have the luxury of their own dedicated clinical unit or full in-house
capabilities and are required to outsource their clinical trials, including bioavailability
(BA) and bioequivalence (BE) studies.
Although generic companies have internal resources for product
development, manufacturing and release testing, they do not have
clinical and bio analytical capabilities.

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Identification of appropriate CROs
• It is important that your CRO has validated corporate procedures for all segments of clinical
study conduct.
• These procedures are used to ensure that all aspects of a study, including but not limited to
clinical conduct, laboratory analysis, data management, biostatistics, pharmacokinetics, and
medical writing, are performed in compliance with Good Clinical Practices (GCP),Good
Laboratory Practices (GLP), and other applicable regulatory practices and guidelines.
Assessment of Capabilities
1. Clinical capabilities
2. Bio analytical capabilities
3. Pharmacokinetic capabilities
4. Timeline assessment

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CRO Qualification
1. Due diligence
• If the pharmaceutical firm has used the CRO in the past, they should objectively evaluate
their past experience with this CRO.
• If the experience was good, the firm should identify those components that were successful
and insure that they are used for their new study.
• However, caution should be exercised and due diligence pursed if the new study requires a
different subject population or analytical technique.
Example:
A CRO may specialize in recruiting healthy male and female
volunteers, but may have difficulty in the recruitment of
postmenopausal females.

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2. Clinical site qualification
The sponsor should conduct a site qualification visit. In addition to a eGCP
site audit, this evaluation should include an assessment of the area
mentioned below;
Clinical site evaluation
• Assess the volunteer (or patient) population pool
• Evaluate CRO procedures for handling an unexpected and serious adverse event (AE)
investigation.
• Assess training records for the clinical team.
• Evaluate CRO's ability to coordinate plasma/urine shipments to
different bio analytical facilities
• Assess ability to coordinate functional handoffs (e.g. Timely delivery
of protocol to clinic, samples to lab, bio analytical data to the
pharmacokineticist)
• Assess clinical project management capabilities

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Clinical data management
• Assess the validation of the data collection system
• Evaluate query generation, SOPS, CRF and database correction, change
control
• Evaluate clinical deliverables, CRFS (CRO or sponsor format) Data Base (when applicable)
• Blood/plasma/urine collection procedures/SOPS and transport procedures to bio analytical
unit.
• Content of the written clinical report (i.e., CRO clinical report to be incorporated into the
final study report)
3. Bio analytical site qualification
• Candidate CROs for bio analytical laboratory work (for drug, metabolite or
biomarker assay) should also be assessed.
• The company audit should also include cGLP compliance and an
assessment of the laboratory’s inspection history. Copies of the inspection
history with all FDA 483s and EIRs should be reviewed.
• Laboratory project manager should be assessed for their ability
to coordinate all processes with client, clinic and
pharmacokinetic.

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4. Pharmacokinetic site qualification
• The pharmaceutical firm should also qualify the CRO site (or department)
that is responsible for PK and statistical analyses and completion of the
final integrated report. During the pharmacokinetic site audit, following
areas should be assessed:
 Qualification of pharmacokinetic and statistical personnel.
 Validation of pharmacokinetic and statistical programs (usually SAS).
 Compliance with 21CFR(code of federal regulation) Part 11. At the time of this
publication, full and complete compliance with Part 11 was not being enforced.
However, the CRO should have a written plan and timeline for bringing all post
laboratory functions into compliance.

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Reference
 http://www.jli.edu.in/blog/what-is-a-contract-research-organization-cro/
 Shargel.L, Kanfer.I, Generic drug product development (solid dosage form), Scale up, post-
approval changes and post-marketing surveillance page no.299
 CONTRACT RESEARCH ORGANIZATIONS: AN INDUSTRY ANALYSIS Maysoun
Dimachkie Masri, Sc.D, MBA, MPH (Corresponding Author) Assistant Professor,
Department of Health Management and Informatics College of Health and Public Affairs,
University of Central Florida HPA II, Suite 214,Orlando, FL 32816-2205

11. THANKS!
Any questions?
You can find me at
» kushalsaha001@gmail.com
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