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The six topics mentioned earlier are presented in Table 2.1 in the form of questions related to each topic. For each topic, additional details, or “points to consider,” are offered along with notes and clarifications as appropriate. The questions, notes, and clarifications are all based on actual inspectional findings from Regulatory Inspectors or points that have been found to directly or indirectly impact compliant and efficient real-world Laboratory Control System operations.

It is envisioned that the below table may be used as a basis for:

 Evaluating your own laboratory's managerial and administrative systems

 Upgrading your own laboratory's managerial and administrative systems

 Establishing your own laboratory's managerial and administrative systems if it is a new laboratory or if you are making substantial changes to an existing Laboratory Control System

Table 2.1 Components of the laboratory managerial and administrative systems sub element.

#	Laboratory managerial and administrative systems sub element topic	Notes and clarifications
2.1	Organizational Structure and Roles and Responsibilities
2.1.1	Are current organization charts available for review and are they accurate?	Organizational charts will be one of the first things an auditor will request when your laboratory is being inspected. Make sure the document is current and correct in order to make a good first impression.
2.1.2	Is there a policy/procedure that defines the responsibility and authority of the Quality Control (QC) unit?
2.1.3	Have the responsibilities of each functional group and supervisor been clearly defined, including testing and operational requirements, Standard Operating Procedures (SOPs), and all other critical functions?
2.1.4	Is an organizational structure in place which is properly staffed to assure that all required testing/monitoring and support activities are performed?	Section 211.25 Personnel qualifications of the Good Manufacturing Practices regulations states “(c) There shall be an adequate number of qualified personnel to perform and supervise the manufacture, processing, packing, or holding of each drug product.” This applies to the laboratory and failing to meet this requirement is often the root cause of many issues which occur in poorly operated QC laboratories.
2.1.5	Is the span of control and authority assigned to the QC laboratory adequate to allow proper execution of these activities?
2.1.6	Is the ratio of supervisors to analyst appropriate? (A ratio of no more than 1 : 8 is recommended)	If a supervisor has to supervise more than eight employees directly, the effectiveness of their ability to do so decreases dramatically.
2.1.7	Are the roles and responsibilities for each position within the laboratory clearly defined?
2.1.8	Are the roles and responsibilities for each position in the organizational chart defined in formal, controlled, accurate, and current job descriptions?	Up until recently, job descriptions were considered the purview of the human resources department and therefore did not fall under the umbrella of GMPs. This has now changed, and the general expectation of regulatory agencies is that job descriptions should be maintained and controlled like any other GMP document.
2.1.9	Are signature authority, responsibility, and accountabilities appropriate and clearly defined?
2.1.10	Do systems exist to enhance communications, understanding, and working relationships between laboratory and Quality Assurance (QA) personnel?	A healthy, respectful relationship between QC and QA will do wonders for everyone's ability to manufacture, test, and, ship product. QC managers should encourage QA personnel to spend time in the laboratory and teach QA personnel as much about product testing and analytical techniques as they can.
2.1.11	Does a personnel performance evaluation system exist, which tracks laboratory personnel strengths and weaknesses and establishes a means to improve technical, administrative, and managerial skills?	Performance evaluation should not be a one-time-a-year event. A good leader will continually evaluate and assist their employees to become the best that they can be.
2.1.12	Does a master testing schedule or similar document(s) exist to ensure smooth and efficient work flow, and minimize laboratory personnel over-commitment?
2.1.13	Are current copies of CV's and resumes for all personnel, including consultants, available for review?
2.2	Training and Qualification
2.2.1	Have the educational, training, and work experience requirements for each laboratory position been clearly defined and do they reflect current standards in the industry?
2.2.2	Is the requirement for training and qualification clearly described in an SOP or similar document for all laboratory managers, supervisors, analysts, support, temporary staff, and consultants?	Training is defined as an activity designed to provide the skills and/or knowledge that individuals need to perform assigned job-related duties and responsibilities.Qualification is defined as the process, including documentation and approval, whereby a person is trained and demonstrates proof-of-proficiency in specified tests, tasks, procedures, or techniques.
2.2.3	Has a training and qualification curriculum been developed for each position that clearly identifies training requirements for all required SOPs and Policies, Test Methods, Safety Procedures, and the GMPs as well as all other internal and external courses or programs?
2.2.4	Is there a system in place (e.g. electronic, paper-based, or hybrid) to capture, track, and manage training and qualification of laboratory personnel?	Electronic training systems should have a set of standard file + curriculum for each unique position on the organizational chart. For example, the position for a laboratory technician responsible for glassware washing should be loaded into the training system as if it was a real person. It will include all the necessary SOPs required for the position, qualification tasks, safety training, etc. This “standard position” will serve as a template. It then lays the basis for an individual's training record, which will grow and change as the employee is trained and qualified in that position.
2.2.5	Does each employee have a training file or similar record within the training system?
2.2.6	Are the training histories for each individual employee kept current?
2.2.7	Have all laboratory personnel been properly trained and qualified?	This point seems obvious; however during auditing it is not unusual to see someone who was “thrown into a position” because of labor shortages, who has never been trained on the tasks they are preforming in the laboratory.
2.2.8	Are the training histories for each individual employee readily available for review?
2.2.9	Is SOP training conducted in a fashion other than “read and understand” as appropriate?	Unfortunately, organizations have a tendency to perform all SOP training in this fashion. It is not effective in many circumstances and the practice should be restricted to review of minor changes on previously trained-on procedures.
2.2.10	Are metrics, related to the execution of training, collected, analyzed, and used to determine the effectiveness of the employee training system in general?
2.2.11	Do the metrics used to evaluate training system effectiveness include the following:	Metrics can take many different forms; these are just a few suggestions.
2.2.11.1	Number of courses completed versus courses scheduled?
2.2.11.2	Percent of training that is overdue?
2.2.11.3	Evaluation of training course content by attendees?
2.2.11.4	Evaluation of instructor effectiveness by course attendees?
2.2.11.5	Evaluation of test questions to determine their appropriateness and effectiveness in evaluating knowledge?
2.2.12	Is there an analyst qualification program (e.g. proof-of-proficiency for laboratory skills) in place?
2.2.13	Has an individual been designated as the training coordinator or manager?	If the training manager or coordinator is not someone with a laboratory background, make sure they are supported by someone who has a science background with hands-on laboratory experience.
2.2.14	Is there evidence of management support for training and training programs?
2.2.15	Does a formal training budget exist?
2.2.16	Do vendor and consultant training records exist?
2.2.17	Is there evidence that newly hired employees are evaluated for skill level, competency, and proof-of-proficiency with respect to laboratory, supervisory, and managerial skills as appropriate?	One of the adages with respect to finding qualified personnel is we hire too quickly and fire too slowly. Take your time when hiring and verify, to the best of your organization's ability that who you are hiring truly does possess the education, training, and experience to do the job you need them to do. Also be aware that no matter how competent and experience a new hire is, it will most likely take them at least six months to come fully up-to-speed within your organization. And if you doubt this, you are fooling yourself.
2.2.18	Is there evidence that newly hired employees are evaluated for their language and literacy skills?	In culturally diverse workplaces, it is not unusual to encounter personnel who are not native speakers, readers, or writers in the primary language used at the facility. Since it is a GMP requirement that procedures exist and such procedures shall be followed, personnel should be evaluated for their ability to read, understand, and execute the SOPs for which are required to be followed in performance of their job responsibilities.
2.2.19	Is there a formal training schedule in place and is it being executed?
2.2.20	Is there evidence of employee re-training and re-qualification?	The GMPs in Section 211.25 (a) state “Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them.” Although this section of the GMPs is targeted to GMP training, it should be expanded to cover the broader arena of job skills in general.
2.2.21	Do managers, supervisors, or training coordinators/managers periodically meet with each employee and review the employee's training record and discuss training and qualification effectiveness and needs?
2.2.22	Is there a positive attitude with respect to training on the part of management and laboratory personnel?	Experience has shown that most employees will openly discuss their pleasure (or displeasure) in the content, effectiveness, and frequency of training and qualification.Employees are also the best to know what needs to be done to upgrade existing training efforts or what new efforts need to be undertaken.
2.3	Laboratory Budgeting, Purchasing, and Requisition
2.3.1	Are levels of approval defined and appropriate for the purchasing and requisitioning needs of the laboratory?	There should be more than one person who can sign, initiate requisitions, and sign purchase orders in the laboratory. This needs to be defined in writing.
2.3.2	Are items purchased from qualified vendors (e.g. reagents, standards, instruments, etc.)?
2.3.3	Does the laboratory have a defined yearly expendables budget?
2.3.4	Is the expendables budget derived from existing data and takes into consideration projected changes in manufacturing volume and its impact on testing workloads?
2.3.5	Does the laboratory have a clearly defined and functional capital expenditure budgeting process?	Capital expenditures include purchasing pieces of equipment and instrumentation such as HPLCs, GCs, balances, etc.
2.3.6	Is the capital budget derived from existing data and take into consideration new product introductions, changes in manufacturing workloads, etc.?	The age of equipment should also be a consideration. Equipment and often the software used to run it need to be replaced from time-to-time. Aging equipment can lead to unnecessary laboratory investigations, which are time-consuming and often not value-added.
2.3.7	Is there a change control system in place to ensure that the purchasing department cannot “swap out” supplies or vendors without involving the laboratory purchasing personnel to prevent inappropriate substitution of materials or equipment?	For example, instances have been observed where the purchasing department, in an effort to save money, has switched vendors who make syringes, which are used to remove samples from dissolution baths. The result was extraneous peaks in the chromatography because the less expensive syringes included a lubricant in the syringe barrel, which was not present in the original validated method syringes.
2.3.8	Does the laboratory have a defined process for requesting and receiving approval to hire new personnel?
2.3.9	Does the laboratory have specific personnel assigned to purchasing and budgeting activities?
2.3.10	Do the personnel assigned to purchasing and budgeting have the proper skills and training to perform planning, budgeting, and purchasing activities?
2.4	Laboratory Administration and Operations
2.4.1	Does the laboratory possess work flow or process diagrams, at least for its primary operations, such as sample management, testing, data review and management, and reporting of results?	Work flow diagrams or process maps are invaluable and lay the basis for efficient operations for most all tasks performed in the laboratory. See the Chapter 2 Appendix (www.wiley.com/go/Bliesner/LabControl_GMPEnvironment) for an example work flow diagram-template.
2.4.2	Does the laboratory have a general administrator, office manager, or similar administrative support person?
2.4.3	Does the administrator, office manager, or similar support person perform or supervise the following activities:
2.4.3.1	Managing work orders for office and laboratory repairs?
2.4.3.2	Overseeing stockroom operations?
2.4.3.3	Supervising requisition of administrative and operational supplies?
2.4.3.4	Managing external contractors and contracts?
2.4.3.5	Managing/enhancing communication between the laboratory and internal/external customers?
2.4.3.6	Supervising laboratory safety training and compliance?
2.4.3.7	Monitoring overtime billing?
2.4.3.8	Initiating capital equipment purchases?
2.4.3.9	Attending production planning meetings?
2.4.3.10	Representing the laboratory at Quality Council, Quality Review, or similar meetings where site-wide quality metrics are reviewed?	It is critical that the QC laboratory be engaged with the other Quality Systems within the organization, particularly Manufacturing and QA.It is not unusual for the QC laboratory to become isolated from the other systems, which leads to an underappreciation of the challenges that exist for running a laboratory. It can also lead to unrealistic expectations regarding the volume of testing, which can be achieved and testing turnaround times, especially at the higher levels of management. Personnel at these levels rarely have laboratory experience and need to be respectfully educated on the nuances and challenges of running a QC laboratory.
2.4.3.11	Collecting, analyzing, reporting, and presenting quality metrics related to the QC laboratory (e.g. laboratory errors, challenges related to test methods, out-of-specification (OOS) and out-of-trend investigations (OOT) investigations, equipment issues, etc.)?	See the Chapter 2 Appendix (www.wiley.com/go/Bliesner/LabControl_GMPEnvironment) for some example metrics.
2.4.3.12	Collecting, analyzing, reporting, and presenting operational metrics related to the QC laboratory (e.g. right-first-time on testing, testing turnaround times, testing backlogs, etc.)?
2.4.3.13	Managing regulatory agency inspections?
2.4.3.14	Managing internal and external audits?
2.4.4	Does the administrator, office manager, or similar support person perform or supervise keeping current with FDA and regulatory related items such as:	FDA has several e-mails feeds to which you can subscribe, including notification of Warning Letters, Guidance Document updates, etc. through the Subscription Management Center: https://www.fda.gov/about-fda/contact-fda/get-email-updates You will receive automatic e-mail notifications to the topics with which you wish to stay current.
2.4.4.1	Recent Warning Letters?
2.4.4.2	Recently posted Form 483 observations?	Electronic reading room for the Centers for Drug Evaluation and Research (CDER) will sometimes post Form 483s from inspections in the website section “Frequently requested or proactively posted compliance records” https://www.fda.gov/drugs/guidance-compliance-regulatory-information/cder-foia-electronic-reading-room
2.4.4.3	New FDA initiatives?	FDA has recently become very active and is spearheading numerous activities which need to be tracked and understood.
2.4.4.4	New or updated Guidance Documents?	https://www.fda.gov/regulatory-information/search-fda-guidance-documents
2.4.4.5	Keeping current with the USP/NF, BP, JP, EP, etc.?	Organizations are encouraged to purchase online subscriptions to the USP/NF and other pharmacopeia as appropriate.
2.4.4.6	Keeping current with industry groups such as American Chemical Society (ACS), American Association of Pharmaceutical Scientists (AAPS), Parenteral Drug Association (PDA), etc.?
2.4.5	Does the administrator, office manager, or similar support person perform or supervise keeping current with industry trends by monitoring or subscribing to:
2.4.5.1	The “Fierce” family of industry blogs (www.fiercepharma.com)?	The “Fierce Family” of blogs includes FiercePharma, FiercePharma Manufacturing, FiercePharmaMarketing, and others.
2.4.5.2	PIC/S? (Pharmaceutical Inspection Convention Pharmaceutical Inspection Co-Operation Scheme)
2.4.5.3	WHO? (World Health Organization)
2.4.5.4	ICH? (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use)	https://www.ich.org/home.html
2.4.6	Does the administrator, office manager, or similar support person supervise administrative service personnel such as maintenance and calibration, laboratory computers, documentation section, training section, etc.?
2.5	Laboratory Chemicals, Solutions, Reagents, and Supplies
2.5.1	Is there a written procedure for receipt and storage of chemicals and reagents?
2.5.2	Are chemicals and reagents properly labeled with date of receipt, date opened, and expiration and re-test dates?
2.5.3	Are laboratory prepared reagents and solutions properly identified (e.g. chemical name or symbol, concentration, date of preparation, initials of the analyst who prepared it, and expiration date)?	Unlabeled solutions are an FDA form 483 favorite citation.
2.5.4	Are records available which document preparation and standardization of volumetric solutions?
2.5.5	Is the frequency of standardization of various reagents described? Is it consistent with the current USP?
2.5.6	Are standardized reagents properly stored to assure integrity?
2.5.7	Does a procedure exist, which describes the generation/purchase, storage, and handling of reagent grade water for laboratory use?	Laboratory water, when opened (exposed to air) will start to grow microbes almost immediately. Therefore, experience has shown that lab water should not be held for greater that 24 hours. If the water is used to prepare chromatographic samples, extraneous peaks resulting from the microbial contamination are possible. This means that water stored in squirt bottles needs to be changed daily.
2.5.8	Are there procedures that describe the preparation of laboratory reagents and cultures?
2.5.9	Are there procedures that describe the maintenance of laboratory reagents and cultures?
2.6	Laboratory Reference Standards and Solutions
2.6.1	Is there a written procedure for ordering and receipt of compendial reference standards and non-compendial reference standards?
2.6.2	Are the primary standards of the current lot listed in the USP, EP, or JP?
2.6.3	Is the receipt of the standards logged?
2.6.4	Are all standards labeled with name, source, lot number, and expiration date?
2.6.5	Do written procedures include provisions for prevention of contamination of primary standards?
2.6.6	Are standards stored in a secured area under environmentally controlled and monitored conditions?
2.6.7	Are procedures for assuring standard integrity available?
2.6.8	Are working or “house” standards checked against primary standards at appropriate intervals?
2.6.9	Are stock solutions appropriately identified, and is their expiration based on their true stability?
2.6.10	Do procedures exist for the certification and use of non-commercially available reference standards?
2.6.11	Do certificates of analysis exist for all reference standards and are these certificates stored as controlled documents?
2.6.12	Have provisions been made for handling, controlled substance reference standards?	This refers to Drug Enforcement Agency (DEA) scheduled materials (e.g. methamphetamine, methadone, etc.).
2.6.13	Does the Reference Standard SOP address (map) proper handling of controlled substance reference standards?