Bringing to market a new food or supplement ingredient involves many challenges stemming from scientific, economic, and regulatory perspectives. One of the challenges sure to be faced is the selection of the Contract Research Organization (CRO) to conduct required safety testing in support of Generally Recognized as Safe (GRAS) determinations, New Dietary Ingredient (NDI) notifications, or other international regulatory submissions.
There a number of reputable CROs throughout the world from which to solicit services. However, not all CROs are created equal. Also, given the complexity of products brought to market in today’s environment, a “one size fits all approach” to safety testing may not be appropriate. The choice of CRO could make or break the chances for commercialization of new products and/or intellectual property.
The CRO selected to conduct safety testing on behalf of your organization is essentially your “partner” in the development of the product. Ensuring that this type of relationship will exist between your organization and the CRO, it is worth asking the Study Director, or other representative of the CRO, a number of questions, prior to soliciting protocols and bids.
Based on the experience of Intertek Cantox in placing studies at CROs, communicating with Study Directors and Study Sponsors, and assisting clients in the preparation of safety dossiers for various product types, we have identified five basic questions that should come to mind as part of the selection process. These questions assume that the safety testing to be conducted would be under Good Laboratory Practice (GLP) conditions and that results of such testing would be used to support the safety assessment and subsequent regulatory approval of the product/chemical in question.
1. Has the CRO been inspected (when and by whom)?
First, any reputable CRO should have undergone inspections by competent authorities. In this regard, the CRO should be able to present copies of their recent inspection reports upon request. Many of the larger CROs, and those performing studies to support registration of food additives or pharmaceuticals in the United States (US), will have been inspected by the US Food and Drug Administration (FDA).
nspection by FDA can take place at CROs worldwide. Similarly, many CROs are inspected by local regulatory authorities (United Kingdom, Germany, Australia, etc.). A lack of such recent inspection could be a sign that the CRO does not conduct a significant number, or the types, of studies used to support product safety assessments and regulatory approval.
2. Can the CRO competently undertake the specific safety testing that you require?
It is unlikely that many CROs would turn away potential clients by indicating that they have little or no experience in conducting the types of studies that you may require. As part of the due diligence, you should ask the CRO to document that they have reasonably good (if not excellent) experience with the species, type of study, route of administration, and any types of special measurements or assays that you may request to “tailor” the study for your needs.
Most labs keep good metrics on the types of studies they have conducted in various species, and sometimes stratify this information based on the different types of test articles (food ingredient, drug, pesticide, etc.) evaluated and the different routes of administration employed (examples: in the diet or drinking water, or by oral gavage). As the Study Sponsor, you should be careful to avoid being on someone’s “learning curve” for a particular study. This is of particular importance if the Sponsor wishes to conduct a “non-standard” study protocol or add a new element to an otherwise standard (e.g., FDA Redbook) protocol.
3. How responsive is the CRO?
Prior to solicitation of protocols and bids, Sponsors should enquire as to who the Study Director might be and whether or not the Study Director is someone who provides active input and is responsive to questions. If you cannot tell at early stages, ask your network of contacts whether they have worked with this Study Director previously.
During early interactions, ask yourself how much input does the CRO provide when the Sponsor asks questions? Does their responsiveness carry into the active phases of the study conduct? That said, if the Sponsor wants to simply hand the safety study over to the Study Director and not be involved at all (i.e., just wait for the draft study report), this is to be distinguished from Sponsors that would like a lot of interaction and assistance from the Study Director.
Based on our involvement over the years, a good CRO experience for the Sponsor depends on a combination of the relationship with the Study Director, practical issues such as technical competence, scheduling and reporting, and ability of the CRO to deal with scientific issues as they arise.
4. Will the CRO be subcontracting out to a third party?
As stated earlier, one cannot expect a CRO to be all things to all Sponsors. All CROs have program/capacity strengths and weaknesses. It is fairly commonplace for CROs to subcontract out portions of the work that goes beyond their capabilities. For example, not all CROs conduct bioanalytical analyses (i.e., analyze blood for levels of test substance and metabolites) in-house.
It is incumbent on the Sponsor to ask what aspects of the work will be conducted in-house, and what will be sub-contracted out. It isn’t always necessary to place an entire program of studies at the same CRO. However, the portion of the work sub-contracted out needs to be at the same standard expected from the CRO.
For example, given that the CRO is qualified to conduct GLP studies, one would wish to be sure that the sub-contracting laboratory is also pre-qualified and/or GLP-compliant. Lack of GLP compliance by the sub-contracted facility may have an impact on the GLP status of the study overall, so understanding the relationships between the different parties is important. In addition, the Study Sponsor needs to have the same level of confidence in the capacities and qualifications of the subcontracted party as they have with their selected CRO.
5. Will the CRO be there when the study is done?
Obviously, it is important to select a CRO that is financially capable of completing a safety study and which would be expected to remain a viable business well after its completion. However, of equal importance is the level of assistance and commitment that the CRO can provide should questions arise regarding the conduct of the study, or interpretation of its results.
Almost inevitably, long after the study is completed, signed off, paid for, and submitted to regulatory authorities in support of an approval process, questions are raised by the regulators. In some cases, it is necessary to recruit staff at the testing facility to help answer these questions either in writing or in person. As a result, it is imperative that the CRO be able to provide such assistance when called upon. Hallmarks of those CROs likely to fit this category include those having Study Directors with senior expertise in the fields of toxicology and pathology, as well as verifiable experience in communicating with regulatory officials.
Part and parcel of the ability of a CRO to fulfill a support role is the state of their record keeping and data retrieval systems. These can be assessed or verified at the time of solicitation of service, perhaps during the conduct of a “pre-study inspection”.
While the CRO is a critical partner in the conduct of safety testing, it our experience that it is also important for the Sponsor to recognize that they are also integral to minimizing the potential for complications that could arise in the safety testing program. For example, test items need to be appropriately characterized and be essentially identical to the product intended for commercialization.
Likewise, the Sponsor should have considered how the test material should be administered, and given prior thought to the rationales behind the selection of dose levels that may required to support safety (e.g., doses that provide large safety margins from human use levels) as well whether sufficient quantities of test material can be made for use by the CRO. As a last thought, it cannot be overstated that as both Sponsor and CRO(s) should play an active part in the conduct of the non-clinical safety testing program; having good partnerships will enable a smoother and more efficient path to market.
Barry S. Lynch, B.Sc., DABT is the Associate Director, Food & Nutrition Group, Intertek Cantox Telephone: 905-542-2900. [email protected]
Valentia Lee-Brotherton, Ph.D. is the director of the Toxicology, Pharmaceutical & Healthcare Group, Intertek Cantox. 905-542-2900. [email protected]
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