D. ORGANIZATION AND
PERSONNEL
(a) ORGANIZATIONAL
CHART
Provide an organizational
flow-chart which shows the responsibilities of key personnel. Key personnel can
be anyone in a decision making capacity who is directly involved in the
development, production, quality control/assurance of a drug product and those
managers above them. Managers involved in the maintenance of the facility should
also be included.
(b) PERSONNEL RESPONSIBILITIES AND
QUALIFICATIONS
Provide the following information
for each employee listed in (a).
a. A brief narrative of their
responsibilities.
b. An educational profile (Curriculum Vitae) including courses taken
outside of formal education to better qualify for his/her assigned
responsibility; and
c. A brief summary of professional experiences.
This information should take up one half (1/2) to a full page for each
employee.
Provide a brief narrative of the responsibilities of key personnel
listed in (a) in the following format.
This section of the DMF should include the curriculum vitae of
all persons listed in (a) and a description of facility employee training
programs.
The curriculum vitae of all persons listed in (a) should include:
a. An educational profile including courses taken outside of formal
education to better qualify for his/her assigned responsibility; and
b. A brief summary of professional experiences.
This information should take up one half (1/2) to a full page.
(c) EMPLOYEE TRAINING
You should have a well documented training program that covers both
general, and specialized training of individuals, along with records of all
training carried out. FDA can request to see this during an inspection. A
training program for all employees should include the following:
a. A background of the industry and its governing legislation;
b. Current Good Manufacturing Practices;
c. General Standard Operating Procedures;
d. Safety
e. Housekeeping.
This section should briefly describe your employee training program.
21 CFR 211.25 dictates the following:
"(a) Each person engaged in the manufacture, process, packing or holding of
a drug product shall have education, training and experience, or any combination
thereof, to enable that person to perform the assigned function. Training shall
be in the particular operation that the employee performs and in current Good
Manufacturing Practice (including the current good manufacturing practice
regulations in this chapter and written procedures required by these
regulations) as they relate to the employees function. Training in 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.
(b) Each person responsible for supervising the manufacture, processing,
packing or holding of a drug product shall have the education, training and
experience, or any combination thereof, to perform assigned functions in such a
manner to provide assurance that the drug product has the safety, identity,
strength, quality and purity that it purports or is represented to
possess.
(c) There shall be an adequate number of qualified personnel to perform and
supervise the manufacture, processing, packing or holding of each drug
product."
A well documented training program, along with records of all training
carried out, must be established. FDA can request to see this during an
inspection. A training program for all employees should include the
following:
a. A background of the industry and its governing legislation;
b. Current Good Manufacturing Practices;
c. General Standard Operating Procedures;
d. Safety; and
e. Housekeeping.
There must also be programs for specialized training of individual
departments and functions. This program and all records of training must also be
documented. Such programs include:
a. Management Training;
b. Training for Quality Control and the individual functions thereof;
c. Training for production supervisors and operators; and
d. Training for maintenance people and their individual functions.
This training must be repeated and updated at defined time intervals, i.e.,
semi-annually or annually. New employees should go through training upon hiring
and should be closely supervised during this period. At this stage, employees
must be thoroughly familiar with the equipment and procedures to be used in
their daily work routine.
Periodic re-evaluation at established time intervals must be done in order
to establish the effectiveness of the training.
The DMF should contain a general description of your training program and a
reference to your training documentation.
(d) CONSULTANTS
Any individual or company whose consultation directly or indirectly
affects the manufacturing process of a drug product, or the drug product itself,
must be listed here.
FOR EXAMPLE:
If consultants are used for your word processing, they need not be listed.
However, consultants should be listed if they are involved in the manufacturing
process, for laboratory work or for process validations.
The description should also indicate:
a. the curriculum vitae and responsibilities of consultants; and
b. that the qualifications of the consultants are approved by the
quality control unit
as per 21 CFR 211.122(c).
If no consultants are used, then a statement to that effect must be given.
(e) CONTRACTORS
In situations where laboratory or manufacturing facilities are less than
adequate in size or equipment, the use of outside contractors is allowed.
However, these contractors must be thoroughly evaluated and validated. An audit
and testing in parallel for a determined period of time may be done to achieve
this.
A written Standard Operating Procedure should be in place for an
original audit and a periodical re-evaluation of all contractors.
Any company or individual contracted for the evaluation or
manufacturing of a drug product or intermediate should be listed here.
(f) QUALITY CONTROL (QC)
This section of the Type I DMF should contain a description of the
responsibilities of QC and a reference to the SOPs describing them.
(g) QUALITY ASSURANCE (QA)
Quality Assurance is the unit responsible for total quality performance as
a company wide concept. The responsibilities of QA should include the
following:
a. Development of Process Validation and Standard Operating Procedures
(SOP).
b. Annual review of Validations and SOPs.
c. Statistical analysis of all data associated with validations.
d. Internal for cGMP compliance.
As with quality control, Standard Operating Procedures must also be
established for the function of Quality Assurance. In this section, please
provide a description of the Quality Assurance unit and hierarchy including a
reference to a Standard Operating Procedure.
(h) EXCLUSION PROGRAM
According to 21 CFR 211.28 (c):
"Any person shown at any time (either by medical examination or
supervisory observation) to have an apparent illness or open lesions that may
adversely affect the safety or quality of drug products shall be excluded from
direct contact with components, drug product containers, closures, in-process
materials and drug products until the condition is corrected or determined by
competent medical personnel not to jeopardize the safety or quality of drug
products. All personnel shall be instructed to report to supervisory personnel
any health conditions that may have adverse affects on drug products."
There should be a written Standard Operating Procedure for the
exclusion of personnel who are ill or have open lesions which may adversely
affect drug products. A statement that such an SOP exists and a reference to it
should be included in this section of the Type I DMF.
Type 2 DMF Guide
