GXP Compliance–Start with the Basics

David Markovitz

David Markovitz

“GXP Training Tips” provides ideas and suggestions associated with the planning, management, and execution of training programs for regulated industries. Reader comments, questions, and suggestions are requested. Case studies illustrating training applications submitted by readers are most welcome. Please send your comments, questions, and suggestions to column coordinator David Markovitz at [email protected] or managing editor Susan Haigney at [email protected].

GETTY IMAGES Key points The following key points are discussed:

oresby/ • Discipline to follow policies and procedures is key to GXP compliance • Reminding people of GXP basics helps to create a habit of arcus M M compliance • GXP training should be conducted on an ongoing basis • Fundamental GXP topics are suggested.

INTRODUCTION The late John Wooden, legendary coach of University of California-Los Angeles’ (UCLA) champion basketball teams in the 1960s and ‘70s, stressed the basics. The first lesson during the first practice of each sea- son was how to put your socks on and how to tie your shoes. The new players were often surprised at this and would complain with phrases like, “Coach, we learned that in kindergarten” and “We already know how to do that.” But Coach Wooden would insist they do it his way, as he had proof that his way reduced the chance of blisters and reduced the chance of tripping on a loose shoelace during a game. Essentially Coach Wooden had a standard operating procedure (SOP) for putting on one’s socks and shoes. He often cited this as one of the major reasons for his record string of championship teams. This was important not only for the two reasons cited above, but also it created the discipline among the players to follow the playbook and listen to their coach. So much of following GXPs in our organizations is the discipline to follow our policies and procedures—our playbook. Most companies that run into trouble with GXP violations with the US Food and Drug Administration and other regulatory bodies find that it is that discipline that is lacking. The policies are in place. The procedures are written and in place. But, for a variety of reasons, people in the organization do not follow the policies or procedures. Reminding people of the basics of GXP is a good place to start in creating a habit of GXP compliance within the organization. Certainly new personnel need to know the basics. But reminding everyone on a regular basis reinforces the importance of GXP compliance.

74 Special Edition: A Roadmap to GMP Compliance Part 2 David Markovitz

Creating a Culture of Quality and GXP Compliance

David Markovitz

“GXP Training Tips” provides ideas and suggestions associated with the planning, management, and execution of training programs for regulated industries. Reader comments, questions, and suggestions are requested. Case studies illustrating training applications submitted by readers are most welcome. Please send your comments to column coordinator David Markovitz at david@gmptraining- systems.com or to coordinating editor Susan Haigney at [email protected].

Actions speak louder than words, and some of the best training occurs by example. Establishing a culture of quality within an organization, starting

GETTY IMAGES with upper most management, creates an environment that inspires employees to take pride in their work and, therefore, follow good practices.

oresby/ Companies that follow GXP regulations understand this concept. Some companies have a culture of quality…and some don’t. To create your own culture of quality, take a look at the companies that are successful, and the arcus M M ones that are not, to see how it’s done.

THOSE WHO DON’T HAVE IT AND DON’T GET IT One generalization we can come to about the companies found in the “Don’t Have It” column is that they do not have a culture of quality in their organization. They have not made GXP a lifestyle. GXP is not part of the fabric of these organizations. These companies can be observed by visiting the US Food and Drug Administration’s website. Companies who don’t put an emphasis on quality are more likely to receive negative attention from FDA. FDA’s website provides information on companies that have run afoul of GXP (1).

FDA Warning Letters FDA Commissioner Dr. Margaret Hamburg, in a speech delivered on Au- gust 6, 2009, stated, “The FDA must be vigilant, the FDA must be strategic, the FDA must be quick, and the FDA must be visible. We must get the word out that the FDA is on the job” (2). Commissioner Hamburg highlighted the following six initial steps designed to hone the effectiveness and timeliness of the FDA’s regulatory and enforcement system (2): • Set post-inspection deadlines • Take responsible steps to speed the warning letter process • Work more closely with FDA’s regulatory partners • Prioritize follow-up on warning letters and other enforcement actions • Be prepared to take immediate action in response to public health risks • Develop and implement a formal warning letter “close-out” process.

These six steps express FDA’s commitment to the warning letter process. It is in a company’s best interest to review other companies’ warn-

Special Edition: A Roadmap to GMP Compliance Part 2 77 David Markovitz

After-Action Reviews—Turning Problems into GXP Learning Points

David Markovitz

“GXP Training Tips” provides ideas and suggestions associated with the planning, management, and execution of training programs for regulated industries. Reader comments, questions, and suggestions are requested. Case studies illustrating training applications submitted by readers are most welcome. Please send your comments, questions, and suggestions to column coordinator David Markovitz at [email protected] or coordinating editor Susan Haigney at [email protected].

INTRODUCTION

GETTY IMAGES Many companies conduct GXP training on a schedule based on the calendar, usually on an annual basis. This approach to training is good,

oresby/ but it is not good enough. Annual training may not take advantage of events or episodes where GXP training can be made more relevant and more meaningful. Training sessions should also be conducted when arcus M M the occasion arises apart from the scheduled training. Training sessions that are more relevant and meaningful will become more memorable, and our GXP programs will become more effective.

caPA Occasions like problems, mix-ups, and errors provide an opportunity for meaningful and memorable discussions. When problems occur, we often invoke caPA. Most of us know the term CAPA (corrective action and preventive action), but by revising the term to “caPA,” the rela- tive importance of preventive action compared to corrective action is emphasized. One important aspect often left out of a caPA project is to use the problem or issue as a learning tool for everyone involved. Do- ing so can lead to a better understanding of the process under review by everyone working on or working in the problem process.

After-Action Review One useful method for gaining additional benefit from our caPA activities and turning them into learning points is through the use of an after-action review. The after-action review is defined as an assessment conducted after a project or major activity that allows employees and leaders to discover and better learn what happened and why. It may be considered a professional conversation about an event that enables employees to understand why things happened during the progression of the process and, most important, to learn from that experience. Here’s how you might use an after-action review as part of the GXP training process. Gather the “right people” to thoroughly discuss the project. This includes the people who work “in the process” (i.e., the operators and other people who actually do the work), along with those people who work “on the process”—the subject matter experts (SMEs) and other people who are expert on the problem situation. Convene all members of the entire group in a comfortable conference room or train-

80 Special Edition: A Roadmap to GMP Compliance Part 2 David Markovitz

It’s All About Trust

David Markovitz

INTRODUCTION GETTY IMAGES “Have a safe flight.” This is what I hear from my wife whenever I leave on a trip that oresby/ involves an airplane. These are the last words from her mouth when we part. I wish she wouldn’t say that, because I can’t think of a response

arcus M that would leave her feeling comfortable. So I just grin and nod my M head to acknowledge her. The only words I can think of to say are these: “I’ll make sure to buckle my seat belt.” “I’ll be sure that my tray table is raised and locked.” “I’ll have my seat in its upright position.” Those are the only things that are in my control as an airline passen- ger to help ensure a safe flight.

Competence–All The Time Consider for a moment the airline industry. What’s the worst thing that can happen when there’s a product failure? The worst thing that can happen is the airplane crashes and people die or are injured. Having a safe flight is really in the hands of the pilot, co-pilot, and the rest of the crew, in the air and on the ground. A safe trip means that the pilot and co-pilot are competent and will be following their procedures whenever they fly—all the time. “Have a safe trip” means that every air traffic controller on duty in and around the air spaces that my airplane will be traveling through or near is competent and will follow their procedures. “Have a safe trip” means that every mechanic or maintenance person who has ever touched that specific aircraft was competent, followed their procedures, and properly documented their work. “Have a safe trip” means that the flight attendants are competent and will be following their procedures at all times.

What About Our Industries? Consider our industries—those industries regulated by the US Food and Drug Administration. What are the worst things that can happen as a result of a product failure? Death or injury. So when your customers buy and use your products or services, they are expecting to “Have a safe flight.”

Trust As airline passengers, we trust the pilots, co-pilots, air traffic control-

Special Edition: A Roadmap to GMP Compliance Part 2 83 Ballard Graham, Richard Poska, Robert Ertmann, and Paul L. Pluta

Preparation, Preparation, and More Preparation

Ballard Graham, Richard Poska, Robert Ertmann, and Paul L. Pluta

“Audit 101” provides useful and practical information that addresses various topics associated with audits. Common-sense suggestions with application to all audits— internal and external, regulatory and non-regulatory, domestic and international—are provided. Examples of actual occurrences are described whenever possible. Reader comments, questions, and suggestions for discussion topics are needed to help us fulfill the column objective. Please send your comments and suggestions to column coordinator Paul Pluta at [email protected].

KEY POINTS The following key points are discussed: • Preparation is a key element in assuring a successful audit. • Specific audit personnel must be identified. These include the primary audit contact, audit coordinator, and other personnel with specific image source getty images audit-related responsibilities and functions. • Activities that are always required for audits must be planned, practiced, and proceduralized as appropriate. These include site visit policy for auditors and other non-employees, document retrieval, review and copying, observation tracking, audit training, and other activities. • Documents must be carefully reviewed before presentation to auditors. • Persons interfacing with auditors must be properly trained. • Logistical considerations including the audit meeting room, support room, auditor parking, security, and other necessities must be planned. • Examples of audit problems due to insufficient planning are provided. • Considerations discussed are applicable to regulatory and non-regulatory audits. • Preparation for an audit is important but must not overshadow the actual objective of an audit—ongoing compliance. An audit will not be successful without a quality culture in the organization that is demon- strably supported by management.

INTRODUCTION There are three keys to assuring a successful audit: preparation, preparation, and more preparation. Preparation must be a key component of the ongoing audit strategy for all audits. Preparation means having all things necessary for a successful audit in place and smoothly functioning ahead of the actual audit. Certain audit personnel and systems will essentially always be part of every audit. These areas must be addressed well ahead of the audit— “well ahead” does not mean the day before agency auditors are expected to arrive. Certain logistical considerations are also important and, if done well, may “set the tone” for a successful audit. This discussion addresses the following critical areas of preparation for a typical audit: • Audit support personnel. Specific audit personnel that will be sup-

Special Edition: A Roadmap to GMP Compliance Part 2 7 Richard Poska and Ballard Graham

FDA 483 Responses— Compliance Considerations

Richard Poska and Ballard Graham

Global Regulatory Viewpoint” addresses various regulatory and compliance topics including newly published regulations from a global perspective. The content in this column is intended to be useful to those who deal with pharmaceutical development, development of CMC dossier sections, and guidances for manufacturing, validation, and CGMPs. The objective of this column: Useful information. Reader comments, questions, and suggestions are requested to help us fulfill our objective for this column. Readers are invited to submit manuscripts for publication in this column. Please contact column coordinator Richard Poska at richard.poska@ abbott.com or journal coordinating editor Susan Haigney at [email protected]. GETTY IMAGES

/ KEY POINTS S K The following key points are discussed in this article: OR

W • US Food and Drug Administration current good manufacturing practices (CGMPs) provide fundamental requirements for pharmaceutical manufac- IMAGE turing • The FDA 483 is the official recording of FDA investigator observations from an FDA inspection • An inadequate inspection response is the primary reason for warning letters being issued in 2008 • FDA’s Anita Richardson (Center for Biologics Evaluation and Research) discussed topics associated with writing an effective Form 483 response at the 5th Annual FDA and the Changing Paradigm for HCT/P Regulation conference in January 2009 • Responses to FDA 483s are not legally required; however, responses are strongly recommended • Responses may mitigate an FDA compliance decision for further action • Responses demonstrate understanding and acknowledgement of the observations • Responses demonstrate a commitment to correct or voluntarily comply with corrective actions • Responses establish credibility with FDA • Failure to respond, inadequate responses, or failure to adhere to promised corrective actions make a firm susceptible to aggressive regulatory or legal actions by FDA such as product seizure, legal injunction, and other actions • After an inspection, an action plan should be quickly developed to address each observation • Effective responses should include a commitment statement from senior leadership, should address each observation separately, should provide corrective action accomplished planned, and should be specific, complete, realistic, and deliver on commitments • Effective responses must be timely, include timeframes for correction, verification methods, monitoring of corrections, and supporting documen- tation • FDA has implemented a Warning Letter Close-out Program • The Enforcement Story, Fiscal Year 2008 summarizes FDA compliance activi-

14 Special Edition: A Roadmap to GMP Compliance Part 2 Barbara Jeroncic

Improved Utilization of Self-Inspection Programs within the GMP Environment–A Quality Risk Management Approach

Barbara Jeroncic

Self-inspection is a well-established and vital part of Irish Medicines Board (IMB) published in the Journal the pharmaceutical quality system. The development of GXP Compliance (3) identifies some of the issues of the International Conference on Harmonisation with current self-inspection programs of pharma- (ICH) Q9 and Q10 guidance documents have intro- ceutical manufacturing companies. A major issue duced an opportunity to improve the design of the discussed was that significant and critical deficien- self-inspection program by application of the qual- cies observed during regulatory inspections were ity risk management (QRM) principles and concepts. not identified and corrected by the companies them- Self-inspection can be designed as a QRM tool used selves via their own self-inspection programs. This to assess the management of current and potential could be due to the fact that for many companies risks to quality and to drive forward continual improve- self-inspection comprises little more than a review of ment. The application of QRM also allows more effi- compliance with current standard operating proce- cient inspection workload and resource management dures (SOPs). Furthermore, its low priority is coupled focusing on those areas within the quality system that with insufficient resources and lack of commitment present higher risk to quality. This article provides from senior management. The interview (3) identifies examples of how QRM could be introduced to main the opportunities for self-inspection to be designed activities within the self-inspection program. The as a formal quality risk management tool capable of article also explores the application of QRM in the identifying and managing risks and driving forward area of self-inspection by pharmaceutical companies tangible and realistic continual improvement. Self- based in Ireland. inspection programs designed in this way can help to demonstrate the effectiveness of the quality system, INTRODUCTION and thus can play an important role in the achieve- Self-inspection is a well-established part of the phar- ment of the reduced regulatory oversight in the in- maceutical quality system. Companies have tradi- spection area (3). tionally been using it as a method for monitoring the This article introduces an innovative self-inspec- implementation and compliance with good manu- tion program design, as a part of quality risk man- facturing practice (GMP) principles, as well as for in- agement, aimed at risk identification and manage- troducing appropriate corrective measures. This role ment as tools for continual improvement. As a part of self-inspection is promoted by the current GMP of the design process, a survey of pharmaceutical legislation and guidance (1). Development of the In- manufacturing companies in Ireland was conducted; ternational Conference on Harmonisation’s (ICH) the findings are reported in this paper. The survey Q10 guide has expanded the role of self-inspection to goal was to explore the practical application of qual- that of an important performance indicator used for ity risk management to self-inspection programs and monitoring the effectiveness of processes and activi- the pharmaceutical industry interest in seeking re- ties within the pharmaceutical quality system. ICH duced level of direct regulatory oversight in the area Q10 promotes the use of self-inspection results as of regulatory inspections. an important input for periodic management review performed to manage, evaluate, and continually im- REALIGNING SELF-INSPECTION AS A QUALITY RISK prove the quality system’s performance (1, 2). MANAGEMENT TOOL An interview with a senior GMP inspector at the Many parts of the European GMP guide (1) are cur-

22 Special Edition: A Roadmap to GMP Compliance Part 2 Paul L. Pluta and Troy Fugate

Effective Training

Paul L. Pluta and Troy Fugate

Welcome to “Effective GMP.” Variation Training API QbR This column discusses specific GMP topics useful to practitioners in compliance EMEA and validation. We intend this column to be a useful resource for daily work ap- Change control plications. The primary objective for this column: Useful information. CALIBRAQbDTIONGHTF The many and varied aspects of GMP, requirements for compliance, and the ramifications of lack of compliance make addressing GMP topics a critical objective for Product compliantsPQ this journal. Recent guidelines have addressed quality systems and risk analysis. These Design space concepts will define the general approach to GMP compliance in the 21st century.

Critical quality attribute s Deviations The key word describing our objective for this column is “effective.” Compliance IQ ICH FMEAProcess design professionals must accomplish the goals and requirements of GMP without excesses

Maintenance ocess parameter s Quality systems or waste—the cost of compliance is an important consideration. Understanding and prioritizing the most critical elements of the various aspects of GMP is fundamental to

Risk analysis ART

W a successful organization.

lidation Va “Effective GMP” addresses GMP topics with these challenges in mind. We intend . STE Veri cation Critical pr WHO S to present various GMP topics clearly and in a meaningful way so that our readers will be able to understand and apply the principles discussed. Reader comments, questions, and suggestions are needed to help us fulfill our objective for this column. Please send your comments and suggestions to column coordinator Troy Fugate at [email protected] or coordinating editor Susan Haigney at [email protected].

INTRODUCTION The cornerstone of compliant operations in a US Food and Drug Adminis- tration-regulated industry is properly trained personnel who successfully perform their day-to-day functions according to approved procedures. Training of personnel is a key element supporting successful performance. Training that is well designed, conducted efficiently, and monitored for effectiveness is fundamental to success. Prioritized and cost-effective training is especially important for obtaining support by senior management. Senior management support is critically important in regards to personnel, time, and resources allotted for training. Training should be established in a manner that works for each particular firm. No one program fits all, so these guidelines should be evaluated and implemented in a manner to ensure success for the specific organization.

DISCUSSION The following key considerations are necessary to accomplish effective training: • Training policy, standards, and procedures documented • Training process strategy and approach defined • Principles of adult learning theory considered • Training needs analyzed and prioritized by risk analysis • Collaboration of affected groups with defined responsibilities and requirements for each group • Trainees and their organizations are “customers” of training • Training appropriate for task • Training materials and methods appropriate and effective • Qualified training personnel

32 Special Edition: A Roadmap to GMP Compliance Part 2 Gordon Welty

Effective Training Reader Q&A—What Are Adult Learning Principles?

Gordon Welty

Variation Training “Effective GMP” discusses specific good manufacturing practice topics useful to API QbR practitioners in compliance and validation. We intend this column to be a useful EMEA resource for daily work applications. The primary objective for this column: Useful Change control information. CALIBRAQbDTIONGHTF Reader comments, questions, and suggestions are needed to help us fulfill our objective for this column. Please send your comments and suggestions to column Product compliantsPQ coordinator Troy Fugate at [email protected] or journal coordinating edi- Design space tor Susan Haigney at [email protected].

Critical quality attribute s Deviations IQ ICH FMEAProcess design KEY POINTS

Maintenance ocess parameter s Quality systems The following key points are discussed in this article: Risk analysis • What are the principles of adult learning? ART

W • Adults learn differently than children lidation Va Critical pr Veri cation . STE • It is important to determine whether employees have really learned WHO S • It is also important to determine whether employees remember the content of their training • Do adults learn differently as they age? • A program logic model (PLM) provides a systematic way to manage training • Adult learning principles can be applied to an organization’s training programs.

INTRODUCTION A previous issue of “Effective GMP” (Journal of GXP Compliance, Summer 2009, Volume 13, Number 3) identifies and briefly discusses the following key points that should be considered in management of a GXP training program: • Training policy, standards, and procedures documented • Training process strategy and approach defined • Principles of adult learning theory considered • Training needs analyzed and prioritized by risk analysis • Collaboration of affected groups with defined responsibilities and requirements for each group • Trainees and their organizations are “customers” of training • Training appropriate for task • Training materials and methods appropriate and effective • Qualified training personnel • Training performance • Training effectiveness monitoring and maintenance • Change training if needed

36 Special Edition: A Roadmap to GMP Compliance Part 2 Gordon Welty

Qualification of Employees for GXP Compliance

Gordon Welty

The US Food and Drug Administration requires all out-of-specification (OOS) findings, and associated ex- employees who work in controlled areas to be trained. cursions as part of investigations. FDA provides latitude for organizations in regulated The first part of this article discusses types of em- industry to develop their own training systems to ployee training, including awareness training, training ensure that employees are appropriately trained for per se (which includes a paper-and-pencil assessment), GXP compliance. This article focuses on the topic employee qualification (i.e., training that includes a of employee qualification, a critical kind of training skill demonstration), and qualification of SMEs. The in regulated industry. It further provides a compre- second part addresses types of qualification, including hensive framework for an organizational approach employee qualification as process and as status, as well to employee qualification. A typology of training is as the use of skill demonstration assessments (SDAs) in presented. Specific employee qualification consider- employee qualification. ations, including employee qualification as process, The third part focuses on the rationale for qualifica- qualification status, and measures to demonstrate tion, highlighting the role the qualification process plays qualification are discussed. Employee qualifica- in deviation investigations and root cause analyses. The tion should be based on a complexity and criticality fourth part considers the criteria for deciding what kind assessment. These concepts demonstrate an orga- of training is appropriate for a specific procedure; this nized approach to employee qualification, compliant depends on the complexity and criticality of the pro- with regulatory requirements and expectations, and cedure and the associated process. The final part de- consistent with modern principles of risk analysis. lineates two other aspects of the qualification process, This is the third of a series of articles on the employee disqualification and employee requalification. development of a GXP training system. The first was “Developing a New Employee Orientation Program for REGULATORY BASIS FOR TRAINING GXP Compliance,” Journal of GXP Compliance, Vol. 13, FDA requires employees in all regulated areas to be No. 3 (Summer 2009), pp. 82-92. The second was trained. For example, 21 CFR 58.29 states “Each in- “Developing a Continuing CGMP Training Program,” dividual engaged in […] a nonclinical laboratory study Journal of GXP Compliance, Vol. 13, No. 4 (Autumn shall have education, training, and experience, or com- 2009), pp. 86-96. bination thereof, to enable that individual to perform the assigned functions” (1). This requirement is re- peated, with slight variation in phrasing, for other regu- INTRODUCTION AND OBJECTIVE lated areas (see Table I). FDA regulations say little more This paper discusses qualification of specific categories about training requirements. According to FDA’s John of employees in a GXP environment. Employee catego- Levchuk, “The FDA has not published a guideline es- ries addressed include production operators and techni- tablishing acceptable procedures for personnel training, cal subject matter experts (SMEs). These personnel are nor is a guideline being planned.” This point was reiter- designated for specific critical tasks in an organization. ated by FDA’s Vasilios Frankos, who stated, “At this time Concepts discussed herein are also applicable to labora- we have no plans to provide companies with training tory analysts. materials for their employees” (2). This paper follows previous published work that dis- Several FDA guidance for industry provide more di- cussed new employee orientation programs, associated rection for training. In the Quality Systems Approach to GXP training, and a continuing current good manufac- Pharmaceutical cGMP Regulations, for example, FDA in- turing practice (CGMP) training program. The present dicates, “Under a quality system, managers are expected paper is useful to anyone working in regulated industry to establish training programs that include the following: with an interest in, and responsibility for, training pro- • Evaluation of training needs grams. It also is useful to quality assurance personnel • Provision of training to satisfy these needs who evaluate training and its relationship to deviations, • Evaluation of effectiveness of training

46 Special Edition: A Roadmap to GMP Compliance Part 2 Gordon Welty

Developing a New Employee Orientation Program for GXP Compliance

Gordon Welty

This article addresses several issues that emerge in with such process and can adjust their performance to the development of a new employee orientation (NEO) meet the expectations. program for GXP compliance. There are two major On the one hand, both sets of expectations for work- sets of organizational expectations for the workplace place performance, compliance and productivity, are performance of a new employee: compliance and operative from the new hire’s first moment on the job. productivity expectations. These expectations are Thus the NEO program is a timely setting for present- operative from the new hire’s first moment on the job; ing these expectations. On the other hand, both sets therefore, NEO is a timely setting for presenting these of expectations are far too extensive to present in detail expectations. This article reviews the employment in the time available for new employee orientation. The lifecycle, the comprehensive process every employee question becomes: How to decide what to cover in the goes through from recruitment to separation, and NEO program? situates NEO in that lifecycle. Next, various features As a preliminary point, the term “new employee” of a typical NEO program are treated. A scenario- should briefly be analyzed. The term is ambiguous. based discussion of regulatory overlap is presented, As Rollag points out, “everyone might agree that an as well as appropriate employee responses. This is arriving recruit is a ‘new employee’ on the first day, followed by an episodic approach to the history of the [but] when do members stop being considered as US Food and Drug Administration. These episodes ‘new employees?’”(1). Likewise, the “new employee” are employed as illustrations of the process of con- is frequently mentioned in discussions of “onboard- tinuous improvement (i.e., identification of problems ing,” even though “The most successful onboarding [deviations], investigation and root cause analysis, and programs […] last one to two years” (2). This ambi- remediations). Finally, several aspects of the organi- guity may impact on the scheduling of new employee zation of the NEO program are presented, including orientation programs (e.g., those that are scheduled on the necessity to coordinate the program across several a biweekly or even monthly basis). Thus the new em- departments. ployee can be on the job for days or weeks before par- ticipating in the NEO program. It will become clear INTRODUCTION that such scheduling practices can present serious GXP A new employee orientation (NEO) program can con- compliance issues or prevent the new hire from being tribute to both GXP compliance and organizational assigned to a limited access area. productivity. New employee orientation can contrib- This article addresses five considerations that emerge ute to GXP compliance by indicating to the new hire in the development of a NEO program for GXP com- or transferring person that the organization (and the pliance. First, the article considers NEO programs in regulatory agency) has a series of expectations for em- terms of what is called the employment lifecycle. Sec- ployee performance in the workplace. These expec- ond, key elements of a typical NEO program, which tations are covered by the GXP regulations, corporate are often overlooked, are described. The third section policies, and local procedures; are written and readily of this article presents a scenario-based discussion of available to employees; and are mandatory. The new regulatory overlap and appropriate employee response. hire or transferred employee may not have experienced Fourth, approaches to presenting the history of the US such regulation in his or her previous position. Food and Drug Administration will be reviewed. Fifth The NEO program can contribute to organizational and finally, several aspects of the organization of the productivity by presenting new hires with the organi- NEO program will be touched on, including the need zation’s process for assessing workplace performance to coordinate the program across several departments. (i.e., employee productivity). The organization’s expectations are summarized in the specifics and cri- NEW EMPLOYEE ORIENTATION AND THE teria of the periodic performance review process. EMPLOYMENT LIFECYCLE Again, new hires or transfers may not have experience New employee orientation is a crucial element in the

56 Special Edition: A Roadmap to GMP Compliance Part 2 Gordon Welty

Developing a Continuing CGMP Training Program

Gordon Welty

This is the second in a series of articles on the devel- and standard operating procedure (SOP) revision, and opment of a GXP training system. The first paper most technical training. In each case, trainees lack skill, was titled “Developing a New Employee Orientation information, or motivation that can be remedied by the Program for GXP Compliance,” and was published in training intervention. the Journal of GXP Compliance, Vol. 13, No. 3 (Summer Training according to the calendar includes much of 2009), pp. 82-92. The present article discusses con- regulatory training—the periodic refresher training that tinuing current good manufacturing practice (CGMP) is mandated in business ethics, non-harassment policies, training in four sections. The first section reviews non-discrimination policies, a number of Occupational statements taken from regulations and guidances about Safety and Health Administration (OSHA) regulations (1), continuing GMP training, made by the US Food and and current good manufacturing practice (CGMP) regula- Drug Administration and other regulatory bodies. The tions. As will become clear in the case of the US Food and interpretive nature of these statements, and the role Drug Administration regulations, refresher training may that risk assessment plays in organizational response to be scheduled more frequently than on an annual basis, gaps (deviations) between the statements and ongoing which is why the regulations and guidance refer to “con- behavior, are stressed. The second section addresses tinuing” CGMP training rather than referring to “annual the topic of individuals who are qualified to deliver the CGMP refresher training.” continuing GMP training, presenting two approaches to The decisions that are made about either kind of qualifying trainers—a formal approach such as a GMP training are informed by an implicit or explicit busi- train-the-trainer program and an experiential approach. ness risk assessment. The level of top-down support While the experiential approach is cheaper than the and the scheduling of continuing CGMP training formal approach, the formal approach has the merit reflect a business risk assessment made by various of reducing variation in employee performance, as well decision makers in the organization. Moreover, deci- as facilitating root cause analysis in case of deviations. sions about the content of the training, in contrast The third section reviews major sources of topics that to mandate and schedule, may also be informed by are available for continuing CGMP training, including a quality risk assessment, an assessment in terms of regulations in 21 CFR 211, written procedures required risk to the safety, identity, strength, purity, and qual- by these regulations, and topics mentioned in FDA ity (SISPQ) of the product (2). guidances, FDA warning letters, and the organization’s Consider an example of business risk assessment, as it own records of deviations, investigations, corrective applies at the program level to continuing CGMP training. actions and preventive actions, and quality complaints. Suppose there is a deviation between the number of em- The final section reviews a major logistical issue in the ployees who have documented attendance at the annual delivery of continuing CGMP training: the frequency CGMP refresher training session and the total number of with which this training should be scheduled. FDA employees who are required by procedure to attend by the recommends training more frequently than just an end of the calendar year. In this case, the alert level is any annual basis. number of employees greater than zero, excluding those on medical leave, etc. The supervisor of an employee who INTRODUCTION has failed to attend by the beginning of the December re- Every organization in regulated industry must train its cess will be alerted by an e-mail message automatically employees. This training is scheduled in several ways. generated by the organization’s learning management sys- There is a basic scheduling distinction between training tem (LMS) (3). Suppose the total number of non-com- that is delivered in response to a perceived deficiency in pliant employees is one. Will this deviation occasion a performance or qualification, and training delivered ac- Notice of Event (NoE), investigation, and corrective action cording to the calendar. Training according to deficiency and preventive action (CAPA)? No. What about 10 em- in performance or qualification includes new employee ployees? Probably not. What about a hundred? Perhaps. orientation (NEO), training for business process redesign Even if it does, will the CAPA be fulfilled? There have

Special Edition: A Roadmap to GMP Compliance Part 2 65 Paul L. Pluta, Editor

First Impressions— The Plant Tour

Paul L. Pluta, Editor

Welcome to “Audit 101.” This feature provides useful and practical information that addresses various topics associated with audits. Audits are an important part of daily operations in the pharmaceutical, medical device, dietary supplement, and other regulated industries. The most critical audits are conducted by government regulators from domestic and international agencies. Audits may also be conducted by industry customers and internal compliance groups. Audits may be planned or unannounced. Government agency auditors may arrive at a site being audited without prior notification and then conduct a thorough audit. Successful manufacturing and quality assurance functions have carefully addressed the various activities associated with audits. These activities have been well planned and developed. They have evolved and been improved based on actual experiences. Successful organizations have policies, procedures, and systems in place that ensure well executed administrations of audits. image source getty images Successful approaches to the various activities associated with audits will be the content of “Audit 101.” We intend “Audit 101” to be a useful resource for readers that will provide valuable information and will help improve audit administration and performance. The sources of information provided in “Audit 101” will not be revealed. Keeping the names of contributors to this feature anony- mous facilitates openness, avoids confidentiality issues, and otherwise enables a free flow of information. Reader comments, questions, and suggestions for discussion topics are needed to help us fulfill the column objective. Please send your comments and suggestions to column coordinator Paul Pluta at [email protected].

KEY POINTS The following key points are discussed: • One of the first significant and critical activities conducted in an audit is the plant tour. The plant tour is a critical activity that must be considered to be of utmost importance. • There are many overlooked items on the plant tour that can negative- ly affect the entire audit. Experience has shown that seemingly trivial items can lead to serious audit consequences and observations. A listing of potential overlooked items is provided. • The plant tour should be carefully planned, evaluated, and practiced long before it is actually needed in an actual audit. • The tour leader is a key person on the tour. The tour leader should speak the native language of the auditor if possible, have good communication skills, and be knowledgeable of all plant operations. Technical competence is important but is not the sole criterion for leading the tour. • Several important considerations such as knowing auditor objectives, plant clothing requirements, and other topics to be addressed during the actual tour are identified. • The plant tour should represent the condition of the entire plant.

Special Edition: A Roadmap to GMP Compliance Part 2 1