Other Laboratory Operations
Food and Drug Administration
For the sake of efficiency and historical perspective, the field components that deal with private laboratories should retain databases or files on each one from which it receives analytical packages. Examples of useful information for these files are described in the following list.
- The name, address, and telephone number of the laboratory and the name and title of key officers or contacts.
- Information on the background, experience, and training of the analysts. (See below for additional guidance.)
- Types of analyses performed by the private laboratory on regulated commodities. Such a list indicates the scope of the laboratory's work.
- Equipment used for conducting the analyses. This aids in determining whether laboratory equipment is present to perform the routine methods.
- Information on the laboratory's internal quality assurance program. This information is useful in evaluating the validity of analytical data generated by the laboratory, although it in no way lessens the need for the QA data for the particular analysis being performed to be submitted as part of the analytical package.
- Reports of FDA's prior contacts with the private laboratory, including previously reviewed packages, reports of on-site assessment visits, correspondence, and summaries of telephone conversations and meetings.
If the reviewing office cannot obtain the information it needs to perform the review of the scientific analytical data generated by the private laboratory, either directly from the laboratory or through the importer/ broker, the analytical packages received from the laboratory will be considered incomplete. Without credible information, there is no way of assuring the scientific integrity of the data being submitted.
One of the topics listed above, information on the background, training, and experience of the analysts bears further discussion. Just as a laboratory is to have the equipment to do its work, so too is it to have properly trained or experienced staff. This should be ascertained before the review of the analytical package is begun.
Often, the analyst's curriculum vita (CV) is attached to the package. If it is not, and the reviewing FDA component doesn't have a prior record in its file, then the laboratory should be called and asked to send or fax it immediately. Attachment 2 is a suggested format for the CV. It may be faxed to the private laboratory.
The CV for each person who participated in the analysis must be submitted or be available on file as needed by each reviewing district or laboratory. It is not sufficient to have only the laboratory director's CV, unless he or she was the only one performing the actual work. A private laboratory director or supervisor may sign a package, but each analyst who performed the actual work also signs (not initial) as well.
Sometimes, a private laboratory will contract its work out to a second laboratory. The package should be shown as being done by the laboratory that actually performed the analysis, not the laboratory that contracted it out. If the paperwork does not make it clear that this was done, the contracting laboratory should be called and asked to submit a CV for that analyst.
The CV provides documentation of the analyst's ability to perform the particular analysis being submitted. A CV is needed that provides evidence of training and experience directly related to the analysis performed by the analyst in question. For example, documentation of an analyst's ability in pesticide analysis is not sufficient for a subsequent submission of a sensory analysis.
Once the CV is received, it is reviewed for adequacy. While there are no requirements for the background of the private laboratory analyst, there should be evidence that they have the education, training, or experience to perform the work. Often, the analysts do not have a college degree and may have received their training on the job. This would not in itself disqualify them from being able to perform the analysis. There should, however, be documentation that they have had preparation for each kind of analysis they submit.
If, as recommended, FDA analysts review the analytical packages, it is further suggested that the CVs be reviewed by a laboratory supervisor, manager, or senior analyst. If the CV is sufficient, the supervisor should write a brief memo saying that the CV provides documentation of the analyst's experience and training in the particular analysis. The CV and memo should be retained for filing. If the CV is not sufficient, the supervisor or designated person should call the private laboratory, explain what additional information is needed, and ask the laboratory to fax or send it. If the laboratory does not provide the information, then the package should be evaluated as unacceptable.
The analytical package consists of the collection report, the private laboratory worksheet, and the laboratory report form (Attachment 3). Since the heart of it is the worksheet, a close technical review of the work performed is needed. FDA laboratory analysts who work in the area of analysis under review are best qualified to perform this review. They are most familiar with current methods, acceptable practices, and quality controls that are needed. Therefore, it is strongly recommended that whenever possible, these packages be sent to the laboratory for review of scientific merit.
A review should begin with the Import Alert. This will provide the reason for detention. The analysis performed corresponds to the problem identified in the Import Alert. For example, if the reason for the Import Alert is the possible presence of a particular pathogen or pesticide, then an analysis for the detection of that analyte is to be performed.
Once the analysis has been established, the reviewer should look at the collection report and determine whether the sample size, type, and method of collection were consistent with resolving the problem. Next, the availability of a CV for the analysts should be ascertained, as described in the section above.
At that point, the review of the worksheet can properly begin. When DWPE began in 1974 (at that time referred to as automatic detention or block listing), among the justifications for its implementation was that it would conserve the agency's laboratory resources and would serve as a reminder to importers that FDA is a regulatory agency, not a quality control laboratory. Thus, responsibility for work previously done by the agency was properly shifted to the importers.
In some senses, then, the private laboratories are doing agency work. They are analyzing regulated commodities and they are to do so with the same care and control with which FDA does its work. This should be kept in mind when reviewing the packages. While the worksheet format used by the private laboratory may differ from FDA practices, all the essential elements that are needed for FDA analyses are to be documented in the package. It would be inconveniently lengthy to itemize each of the elements for all types of analysis, but in general, this is the standard that the packages are to meet.
The following is provided in writing for each analytical package submitted to FDA. Such information helps establish that valid analytical techniques and quality assurance practices were used.
- Identity of the analysts, signatures, and dates on which the work was performed.
- Analytical methods used, references, and any modifications and in-house validations of the methods.
- Signed worksheets containing instrument calibration data, readings and conditions, calculations, quality controls applied, blanks, fortified samples, weighings, dilutions, matrix clean-up procedures, and any other analytical data.
- Calculations presented in a logical manner. Reference to chromatograms and spectra are made in a clear order.
- Source and purity of reference standards, storage conditions, and procedure for preparation.
- Analytical documentation such as chromatograms, charts, graphs, observations, and photographs of thin layer chromatographic plates.
- A copy of the label from the immediate container and any additional labeling needed to evaluate the product.
Attachment 4 is private laboratory package review guide that may be used as an aid in evaluating the analytical worksheets.
Unacceptable versus Violative Results. The purpose of performing the package reviews is to evaluate whether packages are clear, complete, and records of the analytical work that was performed. This review is primarily performed on packages with non-actionable results. It should be noted, however, that the evaluation of the acceptability of a package is separate from its actionable or non-actionable status. A violative package may be acceptable and a non-actionable package may be unacceptable. The validity of a non-actionable package is important because it could result in the release and distribution of harmful product that otherwise would have been detected if the correct method was used or the proper laboratory controls followed, etcetera.
Packages with unacceptable results. The following description of packages that may be unacceptable is meant as guidance only. The list is neither all-inclusive nor exclusive. For example, there may be something that makes a package unacceptable although it is not on the list. The reviewer's judgment, in consultation with his or her supervisor is extremely important in this process.
Many of the items that are not on the list were left off because they can and should be worked out by calling the private laboratory to discuss them. An example of this is uncertainty about the identity of the sample. If there is disagreement between the collection records and the analytical worksheet, this is resolved with the private laboratory before going further. There are occasions when the private laboratory is contacted because the packages are missing essential information, such as legible reports or chromatograms.
- Incorrect results for the particular type of sample or unusual results. An example of this is questionable biochemical reactions obtained during microbiological testing.
- Incorrect amount of sample used for analysis. For example, a method calls for 100g of sample and the private laboratory uses 500g without adjusting the initial extraction volume or the other dilutions. Methods are tested and validated at particular levels and exceeding those levels may invalidate the results.
- Incorrect number of subsamples analyzed. The number of subsamples examined is not consistent or does not follow guidelines. For example, a method may call for the examination of 15 subsamples for Salmonella and the private laboratory only tested 10.
- Failure to determine values for each part of surgical forceps. Both sides of forceps should be tested because there may be a difference (per CDRH). LIB #3750 directs that for separate forged parts, each part should be tested.
- Omission of significant analytical data. For example, biochemical reactions are missing, such as the recording of TSI and LIA reactions for Salmonella. Records of use of controls are absent.
- Omission of quality assurance numbers. For example, omission of several microbiological quality assurance numbers, or a single omission of a quality assurance number for an important component (such as manufacturer's lot number and expiration date for a microbiological test kit).
- Method modifications without indication of validation.
When a package is found to be unacceptable, the compliance officer is responsible for communicating the findings to the importer or broker. He or she may ask the ORA laboratory for assistance in discussing technical issues.
Packages that are acceptable with comments. A package may be acceptable, but contain flaws or weaknesses nevertheless. For instance, the workflow may be difficult to follow or the worksheets may have numerous cross-outs. Sometimes, the reviewer has suggestions that may make future packages stronger or clearer. In these cases, the reviewer should evaluate the package as being acceptable with comments. The reviewer's supervisor (or the reviewer, if so delegated) may call the private laboratory to make these suggestions for improvement. A memo of the telephone conversation should be written to document the discussion and be given to the compliance officer as well as copied to the file.
Packages with violative results. In general, violative packages should not be sent to the laboratory for review since the importer is not asking the agency's permission to admit the entry (at least, not prior to reconditioning). This, however, is subject to local practice in the districts.
Packages with borderline results. If a package is reviewed that has borderline results (for example, if 1 ppm of methyl mercury in swordfish is violative, and the analytical package reports 0.9 ppm methyl mercury) note this in the review of the package. This does not make the package unacceptable, but is simply information for the compliance officer.
Analyses on multiple sub-portions of one entry. Some entries have separate analyses performed on smaller sub-portions of the entry. These sub-portions may correspond to Customs or FDA line numbers, date codes or sizes, for example. This is often true for seafood samples. It may also occur under other circumstances, for example, when ethylene oxide sterilization and subsequent analysis is performed on separate portions of a spice entry. At other times, the reverse situation occurs, that is, one analysis is submitted for several sub-portions. In such cases, each analysis submitted should be evaluated.
Packages from foreign laboratories. These are reviewed using the same criteria as for domestic private laboratories. When a Memorandum of Understanding (MOU) exists, packages should be in accord with the MOU. If the district office has information (such as audit sample results) that the products are violative, the entry in question should be detained, despite certification, and the Office of Enforcement and Import Operations and Office of Regulatory Science(ORS) should be notified. OEIO and ORS will work with the International Affairs staff and the Center offices to resolve the problem.
Timeliness. Since an entry can not be released until the private laboratory analysis has been reviewed, the agency is under the same obligation to complete its review in a timely manner as it is for the products it analyzes. The laboratories should track receipt of analytical packages and the dates the results are sent out. It is suggested that laboratories complete these reviews and report back to the compliance officer within two working days of receipt of the analytical packages. Packages documenting analysis of fresh, perishable products should be completed within one day. The need for additional information, an analyst's CV for example, "re-sets" the clock to the date of receipt of the information.
Reporting the results. ORA laboratories typically report their results to home districts. In this case, however, there are as many as three possibilities for what may be called the home district. The private laboratory may be located in one district, the importer in a second, and the entry may be made in still a third. For the purposes of this guidance document, the district where the entry is being made is considered to be the home district. This is the primary location to which results should be reported. The home district compliance officer is responsible for informing the importer or broker.