Other Laboratory Operations
Food and Drug Administration
- 5.2.1 Preparing for an Inspection
- 5.2.2 Starting an Inspection
- 5.2.3 Regulatory Notes and Exhibits
- 5.2.4 Inspections and Travel
- 5.2.5 Sample Collection
During the course of an analyst's career with FDA, they will often be expected to participate in the inspection of FDA regulated firms. Analysts bring scientific expertise, knowledge, and other skills to an inspection team. Participation may include making and recording observations to evaluate manufacturing processes, practices and conditions; reviewing the firm's records; asking questions of the firm's management or employees; collection of samples; and participation in the discussion of the close out meeting or exit interview with the firm's management. Often the analyst will assist in the preparation of sample collection reports, observations, and establishment inspection reports.
An analyst on a team inspection lends scientific support and technical expertise to the inspection team. The type of team inspection that an analyst will participate in depends upon their area of expertise and the type or complexity of inspection being performed. Chemists, microbiologists, biologists, entomologists, sanitarians, biochemists, organoleptic specialists, and engineers all play an important role in a team inspection.
Prior to beginning a team inspection, preparation for the upcoming inspection is the key. Review the district files of the firm to be inspected and acquaint oneself with the firm's inspectional history, testing practices, and products. Review the previous Establishment Inspection Reports (EIRs) and FDA 483 items. Review the inspectional assignment in FACTS and note what Program Assignment Code (PAC) is listed in the assignment (this will enable the analyst to locate the corresponding Compliance Program). Meet with the Consumer Safety Officer (CSO) and other team members before beginning the inspection. Also review any applicable Laws, Regulations, Compliance Programs, Compliance Policy Guides, and Inspectional Guidance documents relating to the type of team inspection being performed. Do not forget to read the Investigators Operational Manual (IOM). The IOM is the primary source of guidance regarding Agency policy and procedures for establishment inspections and sampling by field investigators and analysts. Knowing what the analyst role is, and what will be expected of each team member is crucial.
In order to prepare for an inspection, an analyst will need to:
- Read the hard copy or FACTS inspectional assignment to determine what is to be covered.
- Review the File Jacket for the previous inspection(s); note previous deficiencies and if there were corrective actions.
- Review previous EIRs and 483s.
- Review the assigned Compliance Program.
- Review the related sections of the CFR.
- Review associated Guidance Documents.
- Ensure sample supplies are present and in good condition if the inspection requires sample collections.
Depending on the type of team inspection, general responsibilities may include reviewing analytical data from production, manufacturing or testing facilities; reviewing and evaluating test methods; and observing actual analytical testing or manufacturing being performed at the facility to assure that good manufacturing practices and good laboratory practices are being used. An analyst may need to evaluate whether laboratory equipment is properly calibrated or qualified. Also, an analyst may need to evaluate sanitation practices and environmental conditions that might affect safe product packaging and production.
During the inspection, an analyst may be asked to collect samples. Sampling operations are carried out using techniques to ensure that the sample is representative of the lot; that the sample of the product is in the same condition as it was before sampling, and that the collection technique does not compromise the compliance status of the lot. The type of samples that may be collected include in-line samples, environmental samples, sanitation samples, water samples, finished product food and drug samples, as well as the various controls associated with these samples. Read the corresponding Compliance Program and the IOM if samples are to be collected. For microbiological inspections, sampling products using aseptic techniques is critical. Aseptic sampling techniques are used to assure that the microbial load of a product is not increased or introduced by a poor sampling procedure. The use of sterile sampling implements and containers, as well as a prescribed sampling method, defines aseptic sampling.
Do remember that during the inspection, safety is paramount. When conducting an inspection or collecting a sample at a firm, make sure that the proper protective clothing and safety equipment are used. The analyst may need to wear a jumpsuit, lab coat, safety glasses, safety shoes, hard hat, hearing protection or respiratory protection. In a sterile drug facility, there may be precise gowning procedures. Guidance should be provided by the firm's management. The analyst can also contact the Regional Industrial Hygienist or ORA Safety and Occupational Health management and discuss any concerns either prior to or during the inspection. The analyst will also need to discuss with the inspectional team and the firm's management any food or drug allergies which may preclude participation in certain aspects of the inspection.
A FDA-482 Notice of Inspection is presented to the most responsible person upon entering a firm. Credentials are also displayed at this time. The analyst will be expected to display their FDA credentials. Securing official credentials through a supervisor may take 1-2 weeks and is done prior to going on inspection. In the case of an international inspection, only credentials are displayed since the Notice is not issued. Analysts must secure an official passport prior to overseas travel. Depending on the country, an official visa may also be needed for entry into the country.The investigator will usually give a brief synopsis of why the inspection is occurring. In the case of a directed or for-cause inspection, the investigator may be vague. Do NOT add to the investigator's comments unless discussed previously.
During the inspection, notes are expected to be recorded. These regulatory notes are recorded in a bound notebook. Note-taking is described in Subchapter 190 Regulatory Notes of the IOM. This subchapter identifies what should be included and what should not be included in inspectional notes or diary notebook. Keep in mind these notes are considered part of the inspection and are subject to the Freedom of Information Action (FOIA). A return address should also be located on the notebook in case it is lost.
An analyst is to document what was reviewed and observed during the inspection in the notebook. The inspectional notebook is factual. The analyst may want to document product names, batch numbers reviewed, names and titles of people spoken to during the inspection and who provided information, SOP numbers of the methods reviewed, raw material, in-process or finished product testing reviewed (e.g., purity assays, dissolution results, objectionable microorganism plate counts) or, the systems reviewed (e.g., sampling, water system testing, or environmental monitoring).
Exhibits are any documents collected during an inspection which are included in the EIR as evidence of observations. Exhibits should contribute to the objective of the assignment and the clarity of the report. In some cases exhibits may be physical materials that constitute evidence for establishing violative conditions. These types of exhibits are prepared and submitted under an INV sample number. In-plant photographs are exhibits as well; however they are submitted under seal in a FDA-525 envelope as an exhibit to the EIR or with a documentary sample.
During the inspection, it is best to collect photocopies of methods, results, standard operating procedures, schedules, etc. that may be used to assist in the description of a process or an objectionable condition. Documents not included in the report should be properly destroyed or shredded. Relate this practice to the firm at the time of collection. In the case of CD-ROMs, the district office may have a policy addressing their disposal or the firm may request the return of the CD-ROM. Either way, state in the report how the CD-ROM was treated.
The "Exhibits" section of the EIR contains a list of all exhibits cited in the EIR. Each exhibit is labeled with the:
- Reference number,
- Name of the firm,
- Dates of the inspection,
- Initials of the team members performing the inspection, and
- Number of pages in the exhibit.
In the EIR, they are listed with their reference number and a title or description. The lead investigator decides how exhibits will be numbered (i.e., whether the analyst's exhibits will be included with those of the investigator and numbered sequentially or included in a separate appended report and numbered separately).
There are many instances when an analyst will be requested to travel outside of the local travel area or to another District. In these instances, the analyst needs to follow the District and Regional policies. If planning to stay overnight, the analyst will need to prepare a Travel Authorization and have it approved PRIOR to the start of the travel.
For on the road inspections, a lap top computer can be a very helpful tool to have at the inspectional location. With a lap top computer, reports can be worked on in the evenings and will allow the analyst to contact various resources for assistance after-hours. Finding resources during the day while at a firm can be quite challenging.
Sampling is outlined in the IOM in SAMPLING. This chapter explains the step by step process for collecting samples. Refer to Subchapter 400 - General prior to the collection. It also describes the types of samples typically collected during an inspection: Official and Documentary. An Official sample is defined in Section 405.1 and Documentary in 405.2. A receipt for sample is issued when collecting physical samples. This receipt is issued after the completion of the inspection but prior to leaving the premises. This process is clearly explained in sections 401.3 Receipt for Sample, 412 Receipt for Samples, 412.5 Prescription Drugs (Non-Controlled), 412.6 Preparation of FDA 484, and 412.7 Routing of FDA 484. Documentary samples usually need the issuance of an affidavit. Affidavits are explained in section 433 AFFIDAVITS. The form typically used is the FDA 463a. Affidavits are crucial since these documents are used to tie all the records collected to the objectionable conditions and show interstate transportation. If an analyst writes an affidavit, be sure to consult the local Investigations or Compliance Branch for the proper style as well as review this section in the IOM.