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Complying with cGMP
 
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Q: What must a manufacturer do to comply with GMP click below for more info
 
requirements for training employees?
 

A: Edward Malawer, Malawer & Associates Consulting, says:

 
For the employees of manufacturers of both drug and dietary  

supplement products, a number of federal regulations and

guidance documents explain the training requirements of
current Good Manufacturing Practices (cGMP) [1-6]. This  

article provides general advice on how to interpret and

comply with those regulations.
 
Some language found in the regulations and guidances is  

open to interpretation. For example, what is an adequate number of staff

members or what constitutes an appropriate combination of education,
training, and experience?  

 
Some of the information is explicit and not open to interpretation, such as
the requirement that you maintain a record of the names, addresses, and
 
qualifications of any consultants and the type of services that they provide.
You must also create written procedures for your processes and document
that you have trained your staff.
   

The FDA publishes summaries of inspectional observations for all product

types under its jurisdiction by fiscal year. The Agency's observations
concerning compliance are instructive. Examples of citations from the 2015
 
fiscal year include: 1) 21 CFR 111.14(b) )—"you did not make and keep
documentation of training"; 2) 21 CFR 211.25(a)—"employees are not given
training in the particular operations they perform as part of their functions or
in cGMP" and "you do not provide the written procedures required by cGMP
regulations"; and 3) 21 CFR 211.25(a)—"GMP training is not conducted on a
 
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continuing basis or with sufficient frequency to assure that employees remain  
familiar with cGMP requirements applicable to them" [7]. Bottle Packaging
  CMC Machinery
GMP Recommendations
Capsule Filling Equipment
In the case of the regulations for drug and dietary supplement products, the CMC Machinery
stated purpose of all training is to enable each individual working in Nilfisk Industrial Vacuums
manufacturing, packaging, warehousing, testing, and quality assurance (QA)
Coating(s) & Equipment
to perform his or her assigned functions in such a manner as to provide
CMC Machinery
assurance that every product meets the requirements for safety, identity, JRS Pharma
strength, quality, and purity that you claim it possesses.
  Contract Formulation/
In planning your training program, you must be conservative when translating Manufacturing & Packaging
Gamlen Tableting
the regulatory requirements and guidance recommendations into training
content so that it can withstand the scrutiny of the FDA when inspections Conveying/Mechanical
occur [8]. Such an approach is the prudent one to avoid inspectional Nilfisk Industrial Vacuums
observations related to training-program deficiencies. VAC-U-MAX
 
Dedusters
To ensure that your program is consistent with the intent of all regulations
CMC Machinery
and guidances, follow my recommendations below. Natoli Engineering
 
Written procedures. Establish procedures for performing training and put Dust Collectors/Filters
them in writing in one or more standard operating procedures (SOPs). Nilfisk Industrial Vacuums
  VAC-U-MAX
Personnel qualifications. Verify that all personnel engaged in manufacturing,
Excipients
packaging, labeling, or holding or in performing quality assurance have the Jost Chemical
education, training, and experience to perform their assigned functions and JRS Pharma
that employees in supervisory roles have appropriately greater levels of
Feeders
education, training, and experience.
VAC-U-MAX
 
Content of training. Create training programs that cover the cGMPs for the Granulators
operations that employees perform, including education on the regulations CMC Machinery
specific to your industry. Focus on the SOPs and technical aspects related to
Inspection Equipment
an employee's position as well as on the defects and errors that he or she
Natoli Engineering
may encounter on the job.
  Metal Detectors/X-Ray
Trainers. Use qualified individuals to conduct all training. Detectors
  CMC Machinery
Frequency of training. Provide training on cGMP continually and often Natoli Engineering
enough so that employees remain familiar with the cGMP requirements
Mixers & Blenders
applicable to them. While the requirements do not specify a cGMP retraining CMC Machinery

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frequency, annual refresher training appears to fit the needs of most

Packaging Equipment
companies and their employees and likely will be acceptable to the FDA.
CMC Machinery
 
Consultants. Make sure that consultants advising on the manufacture, Pneumatic Conveying
processing, packaging, or holding of drug products have sufficient education, CMC Machinery
training, and experience, or any combination thereof, to advise on the Nilfisk Industrial Vacuums
VAC-U-MAX
subject for which you have retained them. Keep records of those consultants'
qualifications. While it would be adequate to retain records of consultants' Services
qualifications, without requiring that they participate in cGMP refresher Gamlen Tableting
training for employees unless they are engaged full-time, some firms prefer Natoli Engineering

to provide a brief, written cGMP orientation to incoming consultants. During Sifters, Screens & Sieves
the orientation, have them acknowledge the orientation with a signature CMC Machinery
before they begin working on site. That procedure is especially important for
Storage/Bulk Handling
service providers who do not typically work in a GMP environment. VAC-U-MAX
 
Recordkeeping. Maintain the appropriate records, including the dates of Tablet Presses
training, its type, the name(s) of person(s) trained, the names of the CMC Machinery
trainers, and the duration of the training. Develop training forms for Gamlen Tableting
Kikusui USA Inc.
individual training and group training and maintain the records, preferably Natoli Engineering
using software created for that purpose. Any company manufacturing
GMP-regulated products that maintains electronic, as opposed to paper, Testing Equipment
Gamlen Tableting
records must additionally be compliant with 21 CFR part 11 regulations. Natoli Engineering
Under such circumstances, a company's GMP training program should include
elements on computer-system validation, electronic signatures, password Tooling
CMC Machinery
control, and audit-trail documentation.
Natoli Engineering
 
Assessment of training. Assess your cGMP training periodically to ensure its Validation
effectiveness and maintain records of those assessments. Typically, CMC Machinery
assessments take the form of a quiz with 10 or more multiple-choice, fill-in-
Weighing Equipment
the-blank, or true-false questions. At the conclusion of a training session, the
VAC-U-MAX
trainer should administer a quiz, correct and score it, and discuss any
incorrect answers with the trainees to ensure they understand a question's
 
GMP principle. Identify an appropriate passing score. In actual practice, the
T&C Solid Dosage
required passing grade ranges from 70 to 100 percent, with 80 percent being
Sourcebook
 

the most common. You must retrain any employees who fail a refresher cGMP
quiz and retest them. Failure to demonstrate understanding of cGMP
principles after remediation should lead to disciplinary action, up to
dismissal.
 
Responsibility for training. None of the regulations or guidances specifies
which function within a company should be responsible for training
employees to work in a GMP environment. The documents generally state
that the trainer must be suitably qualified. You should create a definition of
what suitably qualified means and include it in your training SOPs. Typically,
the training responsibility falls to the QA function; however, if the company is
large, it may have a staff dedicated to training. Personnel in such training
functions usually report to the quality assurance or regulatory department
head. In other companies, the human resources department handles all
training, including for GMP. You may outsource training if your company
doesn't have qualified GMP trainers.
 
A detailed syllabus of initial and on-going training elements to be supplied to
employees is beyond the scope of this article. The nature of those elements
depends on the specific industry because GMP requirements vary
considerably. Guidances on GMP training for both drug and dietary
supplement products are available in the literature [9, 10]. For example, the
training syllabus at a pharmaceutical company should address process
validation but that is not a requirement if the company makes dietary
supplements. Firms in both industries, however, should include an element on
equipment qualification.
 
At a minimum, GMP training must address the specific operations an
employee performs. For example, the regulations would not require a
production employee to receive training in conducting out-of-specification
investigations. Nor would they require a laboratory employee to receive
training in verification protocols for cleaning production equipment. That
said, all initial GMP training should give employees at least an overview of
the principles of GMP for their specific industry.
 
Summary
Some firms consider training a burden that interferes with productivity, but
reports of corrective and preventive actions (CAPAs) often cite human error
as the root cause of deviations. Firms would be better served if they
considered training as one of the most important foundations of GMP. After
all, a good training program leads to a work atmosphere in which all staff
help to oversee compliance with GMPs, which makes good business sense.
 
References

1. 21 Code of Federal Regulations Parts 210 and 211: Part 210-Current

Good Manufacturing Practice in Manufacturing, Processing, Packing, or
Holding of Drugs; General and Part 211-Current Good Manufacturing

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Practice for Finished Pharmaceuticals.

2. 21 Code of Federal Regulations Part 111: Current Good Manufacturing
Practice in Manufacturing, Packaging, Labeling, or Holding Operations
for Dietary Supplements.
3. USP General Chapter <2750> Manufacturing Practices for Dietary
Supplements, USP38/NF34, 2059-2077 (2016).
4. ICH Harmonized Tripartite Guideline Q7: Good Manufacturing Practice
Guide for Active Pharmaceutical Ingredients (November 10, 2000).
5. USP General Chapter <1078>, Good Manufacturing Practices for Bulk
Pharmaceutical Excipients, USP38/NF34, 1128-1148 (2016).
6. The Joint IPEC-PQG Good Manufacturing Practices Guide for
Pharmaceutical Excipients (2006).
7. Fiscal Year 2015 FDA Inspectional Observation Summaries.
8. Malawer EG, A Selected Comparison of 21 CFR Part 111 and USP
General Chapter <2750> as Templates for Good Manufacturing
Practices for Dietary Supplements, Pharm. Engineering, 34(1), 72-77,
(Jan./Feb. 2014).
9. Welty G, Developing a New Employee Orientation Program for GXP
Compliance. J. GXP Compliance,13(3), 82-92 (2009).
10. Welty G, Developing a Continuing cGMP Training Program, J. GXP
Compliance,13(4), 86-96 (2009).

Edward G. Malawer is the owner of Malawer & Associates Consulting, which works
in the areas of cGMP auditing and analytical chemistry, including PAT, test-method
development, and competitive analysis. Since 2009, he has served as lead auditor
for the USP's verification programs for ingredients and dietary supplements. Earlier,
he was vice president of analytical R&D, quality, and product stewardship at ISP, a
supplier of pharmaceutical excipients. He is the author of 37 articles and book
chapters on various analytical and GMP subjects and holds 10 US patents.

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